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1.
Chin J Physiol ; 62(5): 203-209, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31670284

RESUMO

Acute lung injury (ALI) is a common and severe respiratory disease with high morbidity and mortality. Although some progress has been made in the past years, the pathogenesis of ALI is still poorly understood and the therapeutic outcome has still not been significantly improved. It is well-recognized that magnesium sulfate (MgSO4) possesses potent anti-inflammation capacity. The present study was designed to investigate the protective effects of MgSO4 in lipopolysaccharides (LPSs)-induced ALI taken into account that excessive inflammatory response plays critical role in the development of ALI. In this study, Kunming mice were intravenously injected with LPS through tail vein to establish the ALI model and in parallel, A549 cells were used to establish cell model. The lung wet-to-dry weight ratio, malondialdehyde (MDA) levels in lung tissue, lung permeability index, hematoxylin and eosin staining, cytokines in the serum and bronchoalveolar lavage fluid (BALF), neutrophil counts in BALF, LPS-induced A549 cell apoptosis as well as apoptosis-inducing factor (AIF), and Poly(ADP-ribose) polymerase-1 (PARP-1) expression in both mice and A549 cells were detected. Our results demonstrated that MgSO4 significantly attenuated the LPS-induced ALI, oxidative stress (decreased MDA levels), and lung inflammatory response. Moreover, MgSO4 exerted protective effects by mitigating LPS-induced A549 cell apoptosis. Furthermore, MgSO4 decreased the AIF and PARP-1 expression both in vivo and in vitro. Our results, taken together, demonstrated that MgSO4 is a potential therapeutic agent for ALI taken into consideration that MgSO4 is commonly used in clinical settings.


Assuntos
Lesão Pulmonar Aguda , Animais , Líquido da Lavagem Broncoalveolar , Inflamação , Lipopolissacarídeos , Pulmão , Sulfato de Magnésio , Camundongos
2.
Zhonghua Yi Xue Za Zhi ; 99(40): 3176-3182, 2019 Oct 29.
Artigo em Chinês | MEDLINE | ID: mdl-31694111

RESUMO

Objective: To investigate the protective effect of Baicalin on apoptosis induced by lipopolysaccharide in H9C2 cardiomyocytes and its possible mechanism. Methods: In order to establish apoptosis model of H9C2 cardiomyocytes, H9C2 cardiomyocytes were cultured and divided into four groups: the control group; the baicalin group was treated with baicalin at the final concentration of 10µmol/L for 12 hours; the LPS group was stimulated with LPS at the final concentration of 1 µg/ml for 6 hours; The LPS+baicalin group was stimulated with LPS at the final concentration of 1 µg/ml for 6 hours within treated with baicalin at the final concentration of 10µmol/L for 12 hours. Collecting cell samples, CCK-8 (The Cell Counting Kit-8) was used to detect cell activity, and Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) was used to detect the expression levels of apoptosis. Laser Scanning Confocal Microscopy was used to detect the expression levels of store-operated calcium entry in H9C2 cardiomyocytes. Western blot was used to detect the protein expression levels of STIM1, cleaved-caspase3, Bax and Bcl-2. Fluorogenic quantitative PCR was used to detect the mRNA expression level of STIM1. Results: Compared with the control group, LPS-induced H9C2 cardiomyocyte survival rate decreased (P<0.05), the expression level of apoptosis increased (P<0.05), the internal flow of calcium increased (P<0.05), the expression levels of cleaved-caspase3, Bax protein levels increased (P<0.05), Bcl-2 protein level decreased (P<0.05), the expression of STIM1 mRNA and protein level increased (P<0.05). Compared with LPS group, the survival rate of H9C2 cardiomyocytes in baicalin intervention group increased (P<0.05), the expression level of apoptosis decreased (P<0.05), the internal flow of calcium decreased (P<0.05), the expression levels of cleaved-caspase3, Bax protein decreased (P<0.05), and the level of Bcl-2 protein increased (P<0.05), the expression of STIM1 mRNA and protein level decreased (P<0.05). Conclusion: Baicalin may alleviate LPS-induced cardiomyocyte apoptosis by alleviating calcium overload, and improve cell survival.


Assuntos
Miócitos Cardíacos , Apoptose , Cálcio , Flavonoides , Lipopolissacarídeos
3.
J Photochem Photobiol B ; 200: 111635, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31671372

RESUMO

Parkinson disease is one of the most common neurological movement disorders affecting geriatric population. Biosynthesized gold nanoparticles are the ideal alternatives spotlighted by many researchers to treat various diseases. In the present study we synthesized gold nanoparticles using the root extract of Paeonia mountan, woody trees which are used in traditional Chinese medicine to be prescribed for diverse diseases. The synthesis of gold nanoparticles was confirmed with UV-Vis spectroscopic analysis and characterized using FTIR, HR-TEM, EDAX and XRD analysis. The cytotoxicity property of synthesized gold nanoparticles was assessed using MTT assay in the murine microglial BV2 cells. The neuroprotective effect of synthesized gold nanoparticles in inflammatory agent lipopolysaccharides triggered murine microglial BV2 cells was evaluated using nitric oxide, prostaglandin E2 and inflammatory cytokines assays such as IL-6&IL-1ß. Further to confirm in vivo effect of synthesized nanoparticles, the nanoparticles were treated to Parkinson induced C57BL/6 mice. Behavioral, biochemical and molecular analysis were performed to estimate the potency of synthesized gold nanoparticles against the Parkinson induction in mice model. Our characterization results prove the gold nanoparticles synthesized using Paeonia mountan fulfills the requirement of ideal nanodrug and it potentially inhibited the inflammation in in vitro murine microglial BV2. The results of in vivo experiments authentically confirm gold nanoparticles synthesized using Paeonia mountan alleviates the neuroinflammation and improves the motor coordination in Parkinson induced mice.


Assuntos
Ouro/química , Nanopartículas Metálicas/química , Fármacos Neuroprotetores/química , Paeonia/química , Extratos Vegetais/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Antioxidantes/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Química Verde , Lipopolissacarídeos/farmacologia , Masculino , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Microglia/citologia , Microglia/efeitos dos fármacos , Microglia/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Óxido Nítrico/metabolismo , Paeonia/metabolismo , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/patologia , Doença de Parkinson/veterinária , Raízes de Plantas/química , Raízes de Plantas/metabolismo
4.
Adv Exp Med Biol ; 1197: 55-67, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31732934

RESUMO

Gingival epithelium plays a pivotal role in protecting the underlying periodontium from the microbial colonization found in the gingival sulcus. Having an appropriate phenotype displayed by gingival epithelial cells is a critical host component required for protection against bacterial invasion into gingival tissues. In the present study, gingival epithelial homeostasis associated with the CXCL-8/IL-8 chemokine response was investigated in vitro to determine the mechanisms that gingival epithelial cells utilize for sensing gram-positive and gram-negative microorganisms. The findings of this study have demonstrated, by using Fusobacterium nucleatum, a heterogeneity of gingival epithelial cell response by Toll-like receptor (TLR) 2, a lipoprotein sensor. Notably, however, lipopolysaccharide (LPS), a major virulence factor of gram-negative bacteria, is not recognized by gingival epithelial cells unless the LPS is internalized into the cells. Activation of TLR4 in gingival epithelial cells occurs in the endosome, an intracellular event that requires a vesicular acidification to turn on TLR4 signaling, indicating their stringency for fine-tuning a local LPS response. This study has identified a unique LPS sensing mechanism of the oral epithelium to overcome a periodontal infection associated with LPS derived from gram-negative microbes that arises during dysbiosis.


Assuntos
Gengiva , Lipopolissacarídeos , Periodontite , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Gengiva/citologia , Gengiva/imunologia , Gengiva/microbiologia , Humanos , Interleucina-8/imunologia , Lipopolissacarídeos/metabolismo , Periodontite/imunologia , Periodontite/microbiologia
5.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(11): 1110-1115, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31753094

RESUMO

OBJECTIVE: To study the effect of PR-957 on the formation of A1 reactive astrocytes. METHODS: The cerebral cortices of 1-day-old female rats were obtained and cultured for primary astrocytes. These cells were divided into 3 groups: control, lipopolysaccharide (LPS), and LPS+PR-957. The LPS group was treated with LPS (at a concentration of 5 µmol/L) for 48 hours; the LPS+PR-957 group was treated with PR-957 (at a final concentration of 200 nmol/L) for 1 hour and then LPS for 48 hours. Enzyme-linked immunosorbent assay was used to determine the expression of complement 3 (C3, a marker for A1 reactive astrocytes) and tumor necrosis factor alpha (TNF-α). Quantitative real-time PCR was used to determine the relative mRNA expression of glypican-6 (GPC6), SPARC-like 1 (SPARCL1), and lipocalin-2 (LCN2). All the above experiments were repeated three times independently. RESULTS: C3 expression was almost not observed in the control group, but was observed in both the LPS group and the LPS+PR-957 group, with significantly lower expression observed in the LPS+PR-957 group (P<0.05). The expression of TNF-α was consistent with that of C3. Compared with the control group, the LPS and the PS+PR-957 groups had significantly reduced mRNA expression levels of GPC6 and SPARCL1 but significantly increased mRNA expression level of LCN2 (P<0.001). Compared with the LPS group, the LPS+PR-957 group had significantly increased mRNA expression levels of GPC6 and SPARCL1 but significantly reduced mRNA expression level of LCN2 (P<0.001). CONCLUSIONS: LPS can induce the transformation from astrocytes to A1 reactive astrocytes, and PR-957 can inhibit the formation of LPS-induced A1 reactive astrocytes.


Assuntos
Astrócitos , Animais , Feminino , Lipopolissacarídeos , Oligopeptídeos , Ratos , Fator de Necrose Tumoral alfa
6.
Medicine (Baltimore) ; 98(40): e17126, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31577702

RESUMO

BACKGROUND: The aim of this study was to investigate the role of n-acetyl cysteine (NAC) in the lipopolysaccharide (LPS)-mediated induction of tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) synthesis by human periodontal ligament fibroblast cells (hPDLFs). In addition, we aimed to determine the involvement of the nuclear factor-kappa B (NF-κB) pathway in any changes in IL-1ß and TNF-α expression observed in response to LPS and NAC. METHODS: HPDLFs were obtained by primary culture. The culture medium used in this experiment was Dulbecco's Modified Eagle Medium (DMEM low-glucose). Cells were stimulated with various concentrations of NAC or LPS. Cell proliferation was measured at various time-points with the cell Counting Kit 8 (CCK-8) assay. mRNA levels of IL-1ß and TNF-α were determined by real-time quantitative polymerase chain reaction (RT-qPCR) analysis. Protein levels of IL-1ß and TNF-α were measured by enzyme-linked immunosorbent assay (ELISA). Protein and mRNA expression levels of NF-κB were measured by western blot and RT-qPCR. RESULTS: The results showed that LPS treatment in hPDLFs induced mRNA and protein expression of IL-1ß, TNF-α, and NF-κB. However, these effects were eliminated by pretreatment with NAC. Pretreatment with both NAC (1 mmol/L) and BAY11-7082 (10 µmol/L) significantly inhibited the NF-κB activity induced by LPS. CONCLUSION: NAC inhibits the LPS-mediated synthesis of tumor TNF-α and IL-1ß in hPDLFs, through the NF-κB pathway.


Assuntos
Acetilcisteína/farmacologia , Fibroblastos/efeitos dos fármacos , Interleucina-1beta/efeitos dos fármacos , NF-kappa B/efeitos dos fármacos , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Humanos , Interleucina-1beta/biossíntese , Lipopolissacarídeos/farmacologia , NF-kappa B/metabolismo , Ligamento Periodontal , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2966-2971, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602841

RESUMO

To study the effects of saikosaponin b2( SS-b2) on inflammatory factors and energy metabolism against lipopolysaccharide/galactosamine( LPS/Gal N) induced acute liver injury in mice. Mice were randomly divided into normal group( equal amount of normal saline),model group( 100 g·kg~(-1) LPS and 400 mg·kg~(-1) Gal N),low,medium,high dose group of SS-b2( SS-b25,10,20 mg·kg~(-1)·d-1) and positive control group( dexamethasone,10 mg·kg~(-1)). All of the groups except for the normal group were treated with LPS/Gal N though intraperitoneally injection to establish the acute liver injury model. The organ indexes were calculated. The levels of serum transaminases( ALT and AST) and the activities of ATPase( Na+-K+-ATPase,Ca2+-Mg2+-ATPase) in liver were detected. The activity of tumor necrosis factor-α( TNF-α),interleukin-1ß( IL-1ß) and interleukin-6( IL-6) were determined by the enzyme-linked immunosorbent assay( ELISA). The contents of lactate dehydrogenase( LDH) in liver were determined by micro-enzyme method. HE staining was used to observe the histopathological changes of the liver. Histochemical method was used to investigate the protein expression of liver lactate dehydrogenase-A( LDH-A). The protein expressions of Sirt-6 and NF-κB in the liver were detected by Western blot. According to the results,compared with the model group,there were significant changes in organ indexes in the high-dose group of SS-b2( P<0. 05). The level of ALT,AST,TNF-α,IL-1ß,IL-6 and the activities of LDH in serum of mice with liver injury were significantly reduced in the medium and high dose groups of SS-b2( P<0. 01). With the increase of the concentration of SS-b2,the range of hepatic lesions and the damage in mice decreased. The activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in liver of mice were significantly enhanced in each dose group( P<0. 01). The expression of NF-κB in liver tissues was significantly down-regulated in the medium and high dose group( P<0. 01). Meanwhile,the expression of Sirt-6 protein in the liver of mice with acute liver injury was significantly increased in each dose group( P<0. 01).In summary,SS-b2 has a significant protective effect on LPS/Gal N-induced acute liver injury in mice,which may be related to the down-regulation of NF-κB protein expression and up-regulation of Sirt-6 protein expression to improve inflammatory injury and energy metabolism.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Metabolismo Energético , Inflamação/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Animais , Citocinas/metabolismo , Galactosamina , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Camundongos , NF-kappa B/metabolismo , Ácido Oleanólico/farmacologia , Distribuição Aleatória , Sirtuínas/metabolismo
8.
Int J Nanomedicine ; 14: 7309-7322, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571855

RESUMO

Introduction: The only treatment for aseptic loosening is the replacement of the prosthesis through revision surgery. A preventive approach, achieved through anti-inflammatory drugs released from the device, has shown to be a viable strategy; however, the performance of these devices is not yet satisfactory thus further improvements are necessary. Methods: We used titanium nanoparticles as a model for implant surfaces and developed a coating containing dexamethasone (DEX) using layer-by-layer deposition. Results: The amount of deposited drug depended on the number of layers and the release was sustained for months. The efficiency of the released DEX in reducing inflammation markers (tumor necrosis factor alpha and IL-6) produced by human monocytes and macrophages was similar to the pure drug at the same concentration without negative impacts on the viability and morphology of these cells. Conclusion: These coatings were not inferior to medical grade titanium (the standard material used in uncemented devices) regarding their ability to sustain osteoblasts and fibroblasts growth.


Assuntos
Anti-Inflamatórios/farmacologia , Cimentos para Ossos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Liberação Controlada de Fármacos , Nanopartículas/química , Falha de Prótese , Linhagem Celular , Forma Celular/efeitos dos fármacos , Dexametasona/farmacologia , Fibroblastos/efeitos dos fármacos , Humanos , Interleucina-6/metabolismo , Lipopolissacarídeos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Monócitos/efeitos dos fármacos , Nanopartículas/ultraestrutura , Osteoblastos/efeitos dos fármacos , Osteoblastos/patologia , Tamanho da Partícula , Termogravimetria
9.
Analyst ; 144(22): 6721-6728, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31612878

RESUMO

The tympanic membrane (TM) is a dynamic structure that separates the middle ear from the external auditory canal. It is also integral for the transmission of sound waves. In this study, we demonstrate the feasibility of using Raman spectroscopy to identify early chemical changes resulting from inflammation in the TM that can serve as an indicator of acute otitis media. Bacterial lipopolysaccharide (LPS) was injected trans-tympanicaly in a murine model. Presence of inflammatory response was assessed with binocular microscopy, confirmed with histopathology and immunofluorescence staining. Successful discrimination suggesting spectral differences among the control and LPS treated groups was achieved using principal component analysis. Raman imaging revealed major differences in collagen distribution and nucleic acid content. Image segmentation analysis on the trichrome stained tissue sections was performed to corroborate the Raman spectra. The spectral co-localization study suggests changes in the expression of collagen IV specific signals in LPS treated samples. The overall findings of the study support prospective application of RS in the diagnosis and therapeutic monitoring of otitis media.


Assuntos
Otite Média/diagnóstico , Membrana Timpânica/metabolismo , Animais , Feminino , Inflamação/induzido quimicamente , Inflamação/diagnóstico , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Otite Média/induzido quimicamente , Estudo de Prova de Conceito , Análise Espectral Raman/métodos
10.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(9): 1097-1101, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31657332

RESUMO

OBJECTIVE: To investigate the protective effect of carbon monoxide release molecule-2 (CORM-2) on sepsis-induced myocardial dysfunction in rats. METHODS: 140 healthy male Sprague-Dawley (SD) rats were divided into sham operation (Sham) group, model group, CORM-2 pretreatment group, inactivated carbon monoxide release molecule-2 (iCORM) pretreatment group, and dimethyl sulfoxide (DMSO) control group by random number table, with 28 rats in each group. The rat sepsis model was reproduced by intraperitoneal injection of 10 mg/kg lipopolysaccharide (LPS). The rats in the Sham group were injected intraperitoneally with the same dose of normal saline (NS). The rats in the CORM-2 and iCORM-2 pretreatment groups were injected intraperitoneally with 8 mg/kg CORM-2 or iCORM-2 at 1 hour before LPS injection, respectively, and those in the DMSO group were injected intraperitoneally with the same dose of DMSO, but the rats in the Sham group and the model group were not treated after injection of NS or LPS. Twenty rats were randomly selected from each group to observe 10-day survival rate. Transthoracic echocardiography was performed on the remaining 8 rats at 12 hours after modeling, and the left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) were calculated to evaluate heart function. The blood of the inferior vena cava was harvested, then serum myocardial troponin I (cTnI) and brain natriuretic peptide (BNP) levels were measured by enzyme-linked immunosorbent assay (ELISA). Then the rats were sacrificed, and the myocardial tissues were harvested, the pathological morphology and ultrastructure of myocardium were observed. RESULTS: (1) Survival rates: all rats in the Sham group survived; compared with the Sham group, the survival rates of the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group were significantly decreased at 10 days [10% (2/20), 70% (14/20), 25% (5/20), 15% (3/20) vs. 100% (20/20), all P < 0.01]. However, the 10-day survival rate in the CORM-2 pretreatment group was significantly higher than those in the model group, iCORM-2 pretreatment group and DMSO control group (all P < 0.01). (2) Cardiac function: compared with the Sham group, LVEF and LVFS in the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group were significantly decreased, and left ventricular dilatation was obvious, indicating myocardial dysfunction in rats. However, LVEF and LVFS in the CORM-2 pretreatment group were significantly higher than those in the model group, iCORM-2 pretreatment group, and DMSO control group [LVEF: 0.760±0.029 vs. 0.634±0.021, 0.629±0.066, 0.673±0.023; LVFS: (39.32±2.38)% vs. (29.75±1.52)%, (29.61±4.15)%, (32.43±1.66)%, all P < 0.05], and the left ventricular dilatation in the septic rats was attenuated. (3) Myocardial injury markers: compared with the Sham group, serum cTnI and BNP levels were significantly higher in the model group, CORM-2 pretreatment group, iCORM-2 pretreatment group and DMSO control group. However, the levels of cTnI and BNP in the CORM-2 pretreatment group were significantly lower than those in the model group, iCORM-2 pretreatment group and DMSO control group [cTnI (ng/L): 3 283.54±803.50 vs. 6 449.18±1 105.10, 5 919.21±1 068.27, 6 349.80±1 153.08; BNP (ng/L): 3 456.62±905.85 vs. 6 070.18±1 287.62, 5 581.13±1 161.17, 5 974.89±988.89, all P < 0.05]. (4) Myocardial histopathological observation: optical microscope showed that the pathological changes in myocardial tissue of the model group, iCORM-2 pretreatment group and DMSO control group were severe. Transmission electron microscopy showed mitochondrial swelling, and some vacuoles changed. But the myocardial pathological morphology and mitochondrial ultrastructural integrity of the CORM-2 pretreatment group were significantly better than other groups of sepsis. CONCLUSIONS: CORM-2 can attenuate myocardial dysfunction and improve survival rate of septic rats, especially to protect myocardial mitochondrial integrity in sepsis.


Assuntos
Monóxido de Carbono , Miocárdio/metabolismo , Sepse , Animais , Lipopolissacarídeos , Masculino , Ratos , Ratos Sprague-Dawley
11.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(8): 673-681, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31638563

RESUMO

Objective To investigate the impact of the macrophage-derived exosomes on transforming growth factor-ß1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) of lung epithelial cells in an inflammatory environment. Methods The morphology of exosomes derived from THP-1 macrophages was evaluated by transmission electron microscopy, and the biochemistry properties of exosomes were identified by accessing exosome-specific markers including tumor susceptibility gene 101 (TSG101), accessory protein ALG-2 interacting protein X (ALIX), CD81 and CD9 protein, and the calnexin, a negative control marker absent in exosomes, using an immunoblotting assay. The EMT of alveolar epithelial A549 cells was induced by TGF-ß1, and the impacts of exosomes on the EMT of A549 cells was ascertained by comparing cells treated with exsomes derived from LPS-primed THP-1 macrophages and naive THP-1 cells. Results We successfully established an A549 cell EMT model by TGF-ß1 induction and isolated exosomes derived from THP-1 macrophages. In comparison with the exosomes derived from untreated naive THP-1 macrophages, exosomes derived from LPS-primed THP-1 cells exhibited an ability to significantly promote TGF-ß-induced EMT of A549 cells, as determined by a significantly down-regulated E-cadherin, and an dramatically increased expression of proteins in EMT-related signaling including vimentin, alpha smooth muscle actin (α-SMA), TGF-ß1/Smad2/3 signaling proteins Smad2/3 protein and phosphorylated Smad2/3 (p-Smad2/3) and type 1 collagen (Col1). Conclusion Exosomes derived from LPS-stimulated macrophages are able to activate TGF-ß/Smad2/3 signaling, which in turn increase the expression of EMT-related proteins vimentin, α-SMA and Col1 in A549 cells, and subsequently promote EMT in A549 cells.


Assuntos
Transição Epitelial-Mesenquimal , Exossomos , Macrófagos , Fator de Crescimento Transformador beta1 , Células A549 , Transição Epitelial-Mesenquimal/fisiologia , Exossomos/metabolismo , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo
12.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(8): 904-910, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31511209

RESUMO

OBJECTIVE: To investigate the effect of calenduloside E on lipopolysaccharide (LPS)-induced inflammatory response in RAW264.7 cells and explore the underlying molecular mechanism. METHODS: CCK-8 assay was used to examine the effect of different concentrations of calenduloside E (0-30 µg/mL) on the viability of RAW264.7 cells. The release of the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) in RAW264.7 cells in response to pretreatment with 6, 8, and 10 µg/mL calenduloside E for 2 h followed by stimulation with 100 ng/mL LPS was detected using enzyme-linked immunosorbent assay (ELISA). The expression levels of iNOS and COX-2 and the activation of JAK-stats, MAPKs and NF-кB signaling pathways in the treated cells were determined using Western blotting. A reactive oxygen species (ROS) detection kit was used to detect ROS production in the cells, and the nuclear translocation of the transcription factor stat3 was observed by laser confocal microscopy. RESULTS: Calenduloside E below 20 µg/mL did not significantly affect the viability of RAW264.7 cells. Calenduloside E dose-dependently decreased the expression levels of iNOS and COX-2 induced by LPS, inhibited LPS-induced release of TNF-α and IL-1ß, and suppressed LPS-induced JAK1-stat3 signaling pathway activation and stat3 nuclear translocation. Calenduloside E also significantly reduced ROS production induced by LPS in RAW264.7 cells. CONCLUSIONS: Calenduloside E inhibits LPS-induced inflammatory response by blocking ROS-mediated activation of JAK1-stat3 signaling pathway in RAW264.7 cells.


Assuntos
Transdução de Sinais , Animais , Lipopolissacarídeos , Camundongos , NF-kappa B , Ácido Oleanólico/análogos & derivados , Células RAW 264.7 , Espécies Reativas de Oxigênio , Saponinas
13.
Chem Pharm Bull (Tokyo) ; 67(9): 1006-1014, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31474723

RESUMO

Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxide (NO) in RAW264.7 cells induced by lipopolysaccharides (LPS) effectively, but also have high safety in in vitro cytotoxic test, which could be comparable with D104. Molecular docking study on the peroxisome proliferator-activated receptor γ (PPARγ) protein revealed that compounds B12 and B13 can follow the same binding mode with D104, and the carboxyl group of caffeoyl salicylate scaffold might play a key role in the interaction with protein target, which implied the carboxyl group should be retained in the further optimization.


Assuntos
Ácido Clorogênico/química , Óxido Nítrico/metabolismo , Ácido Salicílico/química , Células A549 , Animais , Sítios de Ligação , Sobrevivência Celular/efeitos dos fármacos , Ácido Clorogênico/farmacologia , Humanos , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , PPAR gama/química , PPAR gama/metabolismo , Estrutura Terciária de Proteína , Células RAW 264.7
14.
Zhonghua Shao Shang Za Zhi ; 35(8): 580-586, 2019 Aug 20.
Artigo em Chinês | MEDLINE | ID: mdl-31474037

RESUMO

Objective: To investigate the role and mechanism of nonreceptor tyrosine kinase Tec in the production of pro-inflammatory cytokine interleukin-8 (IL-8) induced by endotoxin/lipopolysaccharide (LPS) in human alveolar epithelial cells A549. Methods: Human alveolar epithelial cells A549 were routinely cultured and passaged in Roswell Park Memorial Institute-1640 medium containing 10% fetal bovine serum. The second or third passage of cells were collected for subsequent experiments. (1) Cells were collected and divided into 6 groups with 4 wells in each group according to the random number table. Cells in blank control group were routinely cultured for 2 h. Cells in simple LPS group were routinely cultured for 1 h and then stimulated by 1 µg/mL LPS for 1 h. Cells in simple LFM-A13 group were cultured with conventional culture medium adding 75 µmol/L LFM-A13 for 1 h and then cultured with replaced conventional culture medium for 1 h. Cells in 25 µmol/L LFM-A13+ LPS group, 75 µmol/L LFM-A13+ LPS group, and 100 µmol/L LFM-A13+ LPS group were cultured with conventional culture medium adding 25, 75, and 100 µmol/L LFM-A13 respectively for 1 h and then all stimulated by 1 µg/mL LPS added into the replaced conventional culture medium for 1 h. The protein expression of Tec in cells of each group was detected by Western blotting, and the content of IL-8 in cell culture supernatant of each group was determined by enzyme-linked immunosorbent assay. (2) Cells were collected and divided into 5 groups with 4 wells in each group according to the random number table. Cells in blank control group were routinely cultured for 2 h. Cells in small interfering RNA (siRNA) control+ LPS group were transfected with empty lentivirus for 10 h and then stimulated by 1 µg/mL LPS added into the conventional culture medium for 2 h. Cells in Tec mus-298 RNA interference (RNAi)+ LPS group, Tec mus-299 RNAi+ LPS group, and Tec mus-300 RNAi+ LPS group were transfected with lentivirus loaded with Tec mus-298 RNAi, Tec mus-299 RNAi, and Tec mus-300 RNAi respectively for 10 h and then stimulated by 1 µg/mL LPS added into the conventional culture medium for 2 h. The protein expression of Tec in cells of each group was detected by Western blotting to screen Tec-siRNA with the best silencing effect on Tec gene. (3) Cells were collected and divided into 4 groups with 4 wells in each group according to the random number table. Cells in blank control group were routinely cultured for 2 h. Cells in virus control group were transfected with empty lentivirus for 10 h and then routinely cultured for 2 h. Cells in simple LPS group were stimulated by 1 µg/mL LPS added into the conventional culture medium for 2 h. Cells in Tec-siRNA+ LPS group were transfected with lentivirus loaded with Tec-siRNA with the best silencing effect on Tec gene for 10 h and then stimulated by 1 µg/mL LPS added into the conventional culture medium for 2 h. The protein expressions of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) MAPK of cells in each group were detected by Western blotting. Data were processed with one-way analysis of variance and the least significant difference-t test. Results: (1) Compared with that of blank control group, the protein expression of Tec of cells in simple LPS group was obviously increased (t=9.72, P<0.05), but the protein expression of Tec of cells in simple LFM-A13 group was not obviously changed (t=4.31, P=0.05). Compared with that of simple LPS group, the protein expression of Tec of cells in 25 µmol/L LFM-A13+ LPS group, 75 µmol/L LFM-A13+ LPS group, or 100 µmol/L LFM-A13+ LPS group was obviously decreased (t=9.72, 9.07, 16.33, P<0.05 or P<0.01). Compared with (189±22) pg/mL of blank control group, the content of IL-8 in culture supernatant of cells in simple LPS group was obviously increased [(214±10) pg/mL, t=2.18, P<0.05], but the content of IL-8 in culture supernatant of cells in simple LFM-A13 group was not obviously changed [(173±43) pg/mL, t=0.64, P>0.05]. Compared with that of simple LPS group, the content of IL-8 in culture supernatant of cells in 25 µmol/L LFM-A13+ LPS group was not obviously changed [(204±38) pg/mL, t=0.54, P>0.05], but the content of IL-8 in culture supernatant of cells in 75 µmol/L LFM-A13+ LPS group and 100 µmol/L LFM-A13+ LPS group was obviously decreased [(144±44), (137±51) pg/mL, t=3.63, 2.55, P<0.05 or P<0.01]. (2) Compared with that of blank control group, the protein expression of Tec of cells in siRNA control+ LPS group was obviously increased (t=14.24, P<0.01). Compared with that of siRNA control+ LPS group, the protein expression of Tec of cells in Tec mus-298 RNAi+ LPS group or Tec mus-299 RNAi+ LPS group was obviously decreased (t=36.03, 18.23, P<0.01), but the protein expression of Tec of cells in Tec mus-300 RNAi+ LPS group was not obviously changed (t=4.08, P>0.05). The protein expression of Tec was the lowest in cells of Tec mus-298 RNAi+ LPS group, so Tec mus-298 RNAi was used in subsequent experiment. (3) Compared with 1.16±0.16 and 0.78±0.11 of blank control group, the protein expressions of p38 MAPK and ERK MAPK of cells in virus control group were not obviously changed (1.66±0.13, 0.89±0.11, t=11.09, 3.60, P>0.05), but the protein expressions of p38 MAPK and ERK MAPK of cells in simple LPS group were obviously increased (2.83±0.29, 1.86±0.37, t=9.70, 7.23, P<0.05). Compared with those of simple LPS group, the protein expression of p38 MAPK and protein expression of ERK MAPK of cells in Tec-siRNA+ LPS group were obviously decreased (0.69±0.16, 1.03±0.24, t=13.78, 4.12, P<0.05 or P<0.01). Conclusions: Tec may mediate the production and release of pro-inflammatory cytokine IL-8 from human alveolar epithelial cells A549 induced by LPS via the p38 MAPK and ERK MAPK signal pathways.


Assuntos
Células Epiteliais Alveolares/metabolismo , Interleucina-8/metabolismo , Proteínas Tirosina Quinases/metabolismo , Células A549 , Humanos , Lipopolissacarídeos , Transdução de Sinais
15.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(8): 983-988, 2019 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-31537224

RESUMO

OBJECTIVE: To explore the immunomodulatory effects of interleukin-17 (IL-17) on acute lung injury (ALI) induced by lipopolysaccharide (LPS). METHODS: Thirty-six SPF-class C57BL/6 mice were divided into normal saline control group (NS group) and LPS-induced ALI model group (LPS group, LPS 5 mg/kg intratracheal drip) according to random number table method, with 18 mice in each group. Six mice were sacrificed at 2, 6 and 24 hours after model reproduction, and peripheral blood, lung and spleen tissues were harvested. After staining with hematoxylin-eosin (HE), the pathological changes of lung tissue were observed under microscope and the infiltration level of lymphocytes, neutrophils and macrophages in the alveolar wall and tracheal wall were detected. Immunohistochemistry was used to detect the protein expression of IL-17 in alveolar wall and tracheal wall, and the correlation between IL-17 expression and lymphocytes, neutrophils and macrophages infiltration in alveolar wall and tracheal wall were analyzed. The level of IL-17 in lung tissue homogenate was determined by enzyme linked immunosorbent assay (ELISA). Flow cytometry was used to detect the proportion of CD4+IL-17+ helper T cells (Th17 cells) in CD4+ T cells in peripheral blood, lung tissue and spleen tissue. RESULTS: (1) Microscopy showed that the lung tissue structure of NS group was basically normal at each time after model reproduction, and there was no obvious inflammatory cell infiltration, while the lung tissue edema and inflammatory reaction were gradually aggravated in the LPS group, and the lung injury score was significantly higher than that in NS group at each time (2 hours: 4.47±1.42 vs. 1.10±0.55, 6 hours: 7.93±2.14 vs. 1.23±0.50, 24 hours: 12.67±2.67 vs. 1.20±0.61, all P < 0.01). (2) Immunohistochemistry showed that the protein expression of IL-17 in alveolar wall and tracheal wall of LPS group increased gradually with time, while that in NS group was negative or weak positive. Quantitative analysis showed that the immunohistochemical staining score of IL-17 protein in alveolar wall and tracheal wall of LPS group were higher than those of NS group (alveolar wall: 2.70±1.40 vs. 0.90±0.37 at 2 hours, 5.10±1.76 vs. 1.17±0.59 at 6 hours, 9.67±1.32 vs. 1.10±0.45 at 24 hours; tracheal wall: 2.87±0.89 vs. 0.90±0.39 at 2 hours, 4.97±1.48 vs. 1.10±0.41 at 6 hours, 8.67±1.54 vs. 1.03±0.29 at 24 hours; all P < 0.05). (3) Correlation analysis showed that the protein expression of IL-17 in alveolar wall and tracheal wall were positively correlated with the degree of lymphocyte, neutrophil and macrophage infiltration (alveolar wall: r value was 0.632, 0.550, 0.466; tracheal wall: r value was 0.695, 0.662, 0.575, respectively; all P < 0.01). (4) IL-17 content (µg/L) in lung tissue homogenate was significantly higher than that in NS group at each time after model reproduction (2 hours: 1.37±0.14 vs. 1.01±0.18, 6 hours: 1.65±0.19 vs. 1.11±0.18, 24 hours: 1.92±0.36 vs. 1.17±0.24, all P < 0.01). (5) The proportion of Th17 cells in the peripheral blood, lung tissue and spleen tissue of the LPS group were higher than those of the NS group at each time after model reproduction [peripheral blood: (2.62±0.62)% vs. (1.42±0.40)% at 2 hours, (3.74±0.43)% vs. (1.27±0.32)% at 6 hours, (4.44±0.65)% vs. (1.59±0.45)% at 24 hours; lung tissue: (2.32±0.44)% vs. (1.50±0.25)% at 2 hours, (3.66±0.36)% vs. (1.33±0.24)% at 6 hours, (4.60±0.54)% vs. (1.60±0.27)% at 24 hours; spleen tissue: (1.49±0.36)% vs. (0.69±0.21)% at 2 hours, (2.58±0.55)% vs. (0.59±0.18)% at 6 hours, (3.76±0.57)% vs. (0.65±0.26)% at 24 hours; all P < 0.01]. CONCLUSIONS: IL-17 is involved in the inflammatory immune regulation of ALI mice.


Assuntos
Lesão Pulmonar Aguda/metabolismo , Interleucina-17/metabolismo , Animais , Lipopolissacarídeos , Pulmão , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa
16.
Inflammopharmacology ; 27(5): 941-948, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31482259

RESUMO

Metformin (MET), a biguanide oral hypoglycaemic agent, recently has been shown to be effective in various conditions other than type-2 diabetes including cancer, stroke, weight reduction, and polycystic ovarian syndrome, to name a few. MET has also possessed antioxidant and antiinflammatory properties by activation of AMPK . This study was aimed at evaluating the effects of MET on lipopolysaccharide (LPS)-induced systemic and neuroinflammation, oxidative stress, and behavioural changes. The study consisted of six groups, where three selected doses of MET (100, 200, and 300 mg/kg) were employed in male Swiss albino mice, with one group of imipramine (IMI), saline, and LPS each. Systemic inflammation was induced by injecting LPS (1.5 mg/kg) by intraperitoneal route. A battery of behavioural tests including open field, forced swim, and tail suspension tests were employed to assess the impact of systemic inflammation on exploratory behaviour and learned helplessness. LPS induced significant immobility with profound symptoms of sickness behaviour. Furthermore, LPS led to significant increase in serum and brain proinflammatory cytokines TNF-α and IL-6; and also increased lipid peroxidation with reduced glutathione levels. Pretreatment of the animals with 100 and 200 mg/kg of MET significantly reduced both systemic and central inflammatory markers along with protecting against LPS-induced oxidative stress. The higher dose, 300 mg/kg of MET was not effective against most of LPS-induced biochemical changes. Our preliminary results from this study suggest the antiinflammatory and neuroprotective effects of MET in LPS-induced model of sickness behaviour and neuroinflammation.


Assuntos
Encéfalo/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Inflamação/tratamento farmacológico , Metformina/farmacologia , Animais , Antioxidantes/metabolismo , Encéfalo/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Glutationa/metabolismo , Inflamação/induzido quimicamente , Inflamação/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos
17.
Hypertension ; 74(4): 843-853, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31476902

RESUMO

Preterm birth is associated with proinflammatory conditions and alterations in adult cardiac shape and function. Neonatal exposure to high oxygen, a rat model of prematurity-related conditions, leads to cardiac remodeling, fibrosis, and dysfunction. TLR (Toll-like receptor) 4 signaling is a critical link between oxidative stress, inflammation, and the pathogenesis of cardiovascular diseases. The current study sought to investigate the role of TLR4 signaling in neonatal oxygen-induced cardiomyopathy. Male Sprague-Dawley pups were kept in 80% oxygen or room air from day 3 to 10 of life and treated with TLR4 antagonist lipopolysaccharide from the photosynthetic bacterium Rhodobacter sphaeroides(LPS-RS) or saline. Echocardiography was performed at 4, 7, and 12 weeks. At 12 weeks, intraarterial blood pressure was measured before euthanization for histological and biochemical analyses. At day 10, cardiac TLR4, Il (interleukin) 18, and Il1ß expression were increased in oxygen-exposed compared with room air controls. At 4 weeks, compared with room air-saline, saline-, but not LPS-RS treated-, oxygen-exposed animals, exhibited increased left ventricle mass index, reduced ejection fraction, and cardiac output index. Findings were similar at 7 and 12 weeks. LPS-RS did not influence echocardiography in 12 weeks room air animals. Systolic blood pressure was higher in saline- but not LPS-RS treated-oxygen-exposed animals compared with room air-saline and -LPS-RS controls. LPS-RS prevented cardiac fibrosis and cardiomyocytes hypertrophy, the increased TLR4, Myd88, and Il18 gene expression, TRIF expression, and CD68+ macrophages infiltration associated with neonatal oxygen exposure, without impact in room air rats. This study indicates that neonatal exposure to high oxygen programs TLR4 activation, which contributes to cardiac remodeling and dysfunction.


Assuntos
Hiperóxia/fisiopatologia , Hipertrofia Ventricular Esquerda/fisiopatologia , Lipopolissacarídeos/uso terapêutico , Receptor 4 Toll-Like/antagonistas & inibidores , Disfunção Ventricular Esquerda/fisiopatologia , Animais , Animais Recém-Nascidos , Citocinas/metabolismo , Modelos Animais de Doenças , Hiperóxia/complicações , Hiperóxia/metabolismo , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/metabolismo , Hipertrofia Ventricular Esquerda/prevenção & controle , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/metabolismo , Disfunção Ventricular Esquerda/prevenção & controle
18.
Life Sci ; 236: 116860, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31518605

RESUMO

AIMS: Intrathecal injection of morphine presents analgesic and antiedematogenic effects in rats. However, it is unknown whether tramadol, which possess a mixed mechanism of action, can also produce analgesic and antiedematogenic effects similarly. MAIN METHODS: Male Wistar rats received carrageenan and LPS in the right knee joint. Tramadol (10 µg) was injected intrathecally 20 min before articular LPS injection. Incapacitation and articular edema were measured 5 h after LPS stimulation. Synovial fluid was collected for leukocyte counting and western blot analysis. Whole joint and lumbar spinal cord were also collected for histology and immunohistochemistry, respectively. Intrathecal pretreatments groups were with the NKCC1 blocker bumetanide, TRPV1 agonist resiniferatoxin, µ-opioid receptor antagonist CTOP and serotonergic neurotoxin 5,7-DHT, all previously to tramadol. KEY FINDINGS: Tramadol treatment caused the reduction of incapacitation and edema. It also reduced c-Fos protein expression in the spinal cord dorsal horn and slightly reduced TNF-α levels in synovial fluid, but neither reduced cell migration nor tissue damage. Bumetanide and resiniferatoxin prevented the analgesic and antiedematogenic effects of tramadol. CTOP prevented the analgesic and the antiedematogenic effects, but 5,7-DHT prevented only tramadol-induced analgesia. SIGNIFICANCE: Spinal NKCC1 cotransporter and peptidergic peripheral afferents seem to be important for the analgesic and antiedematogenic effects of tramadol, as well as µ-opioid receptor. However, the monoamine uptake inhibition effect of tramadol seems to be important only to the analgesic effect.


Assuntos
Analgésicos Opioides/administração & dosagem , Artralgia/prevenção & controle , Artrite Experimental/complicações , Artrite Reativa/complicações , Edema/prevenção & controle , Lipopolissacarídeos/toxicidade , Tramadol/administração & dosagem , Animais , Artralgia/etiologia , Artralgia/patologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/fisiopatologia , Artrite Reativa/induzido quimicamente , Artrite Reativa/fisiopatologia , Modelos Animais de Doenças , Edema/etiologia , Edema/patologia , Injeções Espinhais , Masculino , Ratos , Ratos Wistar
19.
Life Sci ; 236: 116865, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31525428

RESUMO

AIMS: Endothelial dysfunction is one of the earliest symptoms in septic patients and plays an important role in the cardiovascular alterations. However, the endothelial mechanisms involved in the impaired sympathetic regulation of the cardiovascular system are not clear. This study aimed to determine the role of the endocardial endothelium (EE) in the cardiac ß-adrenergic (ß-AR) remodeling at the early phase of endotoxemic shock. MAIN METHODS: Rats received either lipopolysaccharide (LPS) or saline (control) intravenously. Three hours later, ß-AR cardiac contractility was evaluated on papillary muscles with or without a functional EE. KEY FINDINGS: Isoproterenol-induced contractility was strongly increased in papillary muscles from LPS rats. A similar increase was observed with a ß1-AR stimulation, whereas ß2-AR and ß3-AR produced similar contractility in control and LPS treatments. The removal of the EE did not modify ß1-AR-induced contractility in controls, whereas it abolished the increased ß1-AR response in LPS-treated muscles. In LPS-treated papillary muscle, the increased ß1-AR-induced contractility was not modified by pretreatment with a NOS inhibitor or an endothelin receptor antagonist. Conversely, the increased ß1-AR-induced contractility was abolished by indomethacin, a non-selective cyclooxygenase (COX) inhibitor, as well as by selective inhibitors of COX1 and COX2. An early treatment with indomethacin improved the survival of LPS rat. SIGNIFICANCE: Our results suggest that the EE is involved in the increased cardiac ß1-AR contractility in the early phase of endotoxemic shock. This effect is mediated through the activation of COX1 and COX2 and suggests these may be novel putative therapeutic targets during endotoxemic shock.


Assuntos
Ciclo-Oxigenase 1/metabolismo , Endotélio Vascular/fisiopatologia , Endotoxemia/fisiopatologia , Proteínas de Membrana/metabolismo , Contração Miocárdica , Músculos Papilares/fisiopatologia , Receptores Adrenérgicos beta 1/metabolismo , Animais , Modelos Animais de Doenças , Endotoxemia/induzido quimicamente , Lipopolissacarídeos/toxicidade , Masculino , Ratos , Ratos Sprague-Dawley
20.
J Agric Food Chem ; 67(42): 11627-11637, 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31553177

RESUMO

Liver diseases alter the gut microbiota, but several lactic acid bacteria can reduce the degree of liver damage. The present study investigated whether Lactobacillus buchneri TCP016 reduces the degree of liver damage by modifying the gut microbiota via its exopolysaccharides (EPSs). First, it was illustrated that the main EPS (EPS016; molecular weight = 8.509 × 104 Da) comprised rhamnose, xylose, glucosamine, glucuronic acid, galactose, galacturonic acid, glucose, and mannose in molar ratios of 9.2:3.9:3.8:2.8:2.1:2.0:1.6:1.0. Our data showed that EPS016 alleviated the increase in plasma and hepatic enzyme and cytokine levels, increased superoxide dismutase and glutathione activity, and alleviated bacterial translocation to the liver and mesenteric lymph nodes in vivo. Furthermore, EPS016 ameliorated intestinal mucosal injury and gut flora dysbiosis, thereby decreasing the enrichment of Helicobacteraceae, Lachnospiraceae, and Enterobacteriaceae and increasing the abundance of Lactobacillus, Rikenellaceae, Bacteroidaceae, Bacteroidales_S24-7_group, and Prevotellaceae. These findings indicated that EPS016 inhibits lipopolysaccharides/d-galactosamine-induced liver injury and improves the modification of the gut microbiota.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Lactobacillus/química , Hepatopatias/tratamento farmacológico , Polissacarídeos Bacterianos/administração & dosagem , Animais , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/isolamento & purificação , Bactérias/metabolismo , Feminino , Galactosamina/efeitos adversos , Humanos , Lactobacillus/metabolismo , Lipopolissacarídeos/efeitos adversos , Hepatopatias/etiologia , Hepatopatias/microbiologia , Camundongos Endogâmicos BALB C , Polissacarídeos Bacterianos/química , Polissacarídeos Bacterianos/metabolismo
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