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OBJECTIVE: To explore the potential mechanism of Yougui Wan on deformed lumbar intervertebral disk structure in rats. METHODS: Thirty male Sprague-Dawley rats were randomly divided into 3 groups, with 10 rats in each group. The animals in the blank control group were healthy rats without specific treatment, and those in the model group and traditional Chinese medicine (TCM) group were used to establish the intervertebral disk degeneration (IDD) model by puncturing the annulus. Four weeks after modeling, rats in the TCM group were administered Yougui Wan by gavage for 2 consecutive weeks. Serum interleukin-6 (IL-10), macrophage migration inhibitory factor (MIF) and tumor necrosis factor alpha (TNF-α) levels were measured by ELISA, and the protein expression levels of collagen II and Notch1 in intervertebral disk tissues were examined by Western blotting. Apoptosis was detected by the TUNEL method. RESULTS: Compared with those in the blank group, IL-10, MIF and TNF-α levels in the model group and TCM group were increased (P < 0.05), the protein expression levels of collagen II were decreased, and the protein expression levels of Notch1 were increased. Compared with those in the model group, the levels of IL-10 in the TCM group were increased (P < 0.05), the levels of MIF and TNF-α were decreased (P < 0.05), the protein expression levels of collagen II were increased, and the protein expression levels of Notch1 were decreased. CONCLUSION: Yougui Wan can inhibit the inflammatory response in IDD rats, reduce the degradation of extracellular matrix, reduce apoptosis in nucleus pulposus cells, and alleviate intervertebral disk degeneration. The mechanism may be related to the regulation of the Notch signaling pathway.
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Medicamentos Herbarios Chinos , Degeneración del Disco Intervertebral , Masculino , Ratas , Animales , Degeneración del Disco Intervertebral/tratamiento farmacológico , Interleucina-10 , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa , ColágenoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Yi Qi Huo Xue Fang (YQHXF) is an effective formula for treating cerebral ischemic stroke (CIS). However, its active ingredients and mechanism of action remain unclear. AIM OF THE STUDY: This study aimed to reveal the mechanism of action of YQHXF in the treatment of ischemic stroke based on network pharmacology and experimental validation. MATERIALS AND METHODS: This study identified the chemical components in YQHXF and the components absorbed by rat serum based on UPLC-Q-TOF/MS technology and used network pharmacology to predict key candidate targets. A protein-protein-interaction (P-P-I) network was constructed using String 11.0 database and Cytoscape, and R software for gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. Finally, molecular docking combined with animal experiments was used to verify network pharmacology results. RESULTS: This study identified and confirmed 36 chemical components of YQHXF and five chemical ingredients that were absorbed into the blood of rats and screened 66 key candidate targets. All targets in the P-P-I network were mainly related to inflammation and vascular processes. KEGG enrichment results revealed that these 66 key candidate targets were primarily involved in the "AGE-RAGE signaling pathway," "TNF-α signaling pathway, and "T cell receptor signaling pathway." Molecular docking results revealed that Prostaglandin-endoperoxidase synthase 2(PTGS-2), Nitric oxide synthase, endothelial (NOS3), and peroxisome proliferator-activated receptor gamma (PPARG) were more stably bound to their active ingredients. Animal experiments demonstrated that YQHXF promoted M2 polarization, inhibited M1 polarization in microglia, and promoted angiogenesis, which may be related to the PPARG pathway. CONCLUSION: This study revealed the key active components and effective targets of YQHXF, identified the mechanism of action of YQHXF, laid the foundation for further research on YQHXF, and provided ideas for developing new drugs for CIS.
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Productos Biológicos , Medicamentos Herbarios Chinos , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Ratas , Simulación del Acoplamiento Molecular , Farmacología en Red , PPAR gamma , Accidente Cerebrovascular/tratamiento farmacológico , Ciclooxigenasa 2 , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Chronic stress induces depression- and anxiety-related behaviors, which are common mental disorders accompanied not only by dysfunction of the brain but also of the intestine. Activating transcription factor 4 (ATF4) is a stress-induced gene, and we previously show that it is important for gut functions; however, the contribution of the intestinal ATF4 to stress-related behaviors is not known. Here, we show that chronic stress inhibits the expression of ATF4 in gut epithelial cells. ATF4 overexpression in the colon relieves stress-related behavioral alterations in male mice, as measured by open-field test, elevated plus-maze test, and tail suspension test, whereas intestine-specific ATF4 knockout induces stress-related behavioral alterations in male mice. Furthermore, glutamatergic neurons are inhibited in the paraventricular thalamus (PVT) of two strains of intestinal ATF4-deficient mice, and selective activation of these neurons alleviates stress-related behavioral alterations in intestinal ATF4-deficient mice. The highly expressed gut-secreted peptide trefoil factor 3 (TFF3) is chosen from RNA-Seq data from ATF4 deletion mice and demonstrated decreased in gut epithelial cells, which is directly regulated by ATF4. Injection of TFF3 reverses stress-related behaviors in ATF4 knockout mice, and the beneficial effects of TFF3 are blocked by inhibiting PVT glutamatergic neurons using DREADDs. In summary, this study demonstrates the function of ATF4 in the gut-brain regulation of stress-related behavioral alterations, via TFF3 modulating PVT neural activity. This research provides evidence of gut signals regulating stress-related behavioral alterations and identifies possible drug targets for the treatment of stress-related behavioral disorders.
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Factor de Transcripción Activador 4 , Tálamo , Masculino , Animales , Ratones , Factor de Transcripción Activador 4/metabolismo , Tálamo/metabolismo , Neuronas/metabolismo , Ratones Noqueados , Colon/metabolismoRESUMEN
Renal cell carcinoma is abbreviated as renal carcinoma, and its clinical symptoms are basically hematuria, lumbago, and abdomen bump. As people's lifestyles change, the incidence of renal carcinoma continues to rise due to factors such as smoking and obesity. At present, surgical treatment is mostly used in clinical practice. Traditional open radical nephrectomy (ORN) is one of the main methods for clinical treatment of renal carcinoma. However, due to its large wound and large amount of intraoperative blood loss, the renal function of patients after surgery is poor, which is not conducive to the postoperative recovery of patients. Retroperitoneal laparoscopic radical nephrectomy (RLRN) has been widely used in the surgical treatment of renal cancer due to its advantages of small wound, less bleeding, and rapid recovery. The purpose of this study was to investigate the efficacy of RLRN in the treatment of renal cancer patients and its effect on renal function and to analyze the related factors affecting postoperative recurrence of patients. We adopt ORN and RLRN, two kinds of treatment, in patients with renal cancer surgery way, contrast analysis of the two groups of operation time, intraoperative blood loss, postoperative intestinal function recovery time, drainage tube indwelling time, length of hospital stay, and other clinical indicators and renal function indexes and use the single factor analysis and multifactor analysis, the relevant factors that affect kidney cancer patients with postoperative recurrence. The results showed that, compared with ORN treatment, RLRN treatment of renal cancer patients has a short operation time, less trauma, quick recovery after surgery, and fewer complications and can effectively alleviate the renal function injury and the body's inflammatory response, which is worthy of promotion. Postoperative recurrence was related to age, tumor diameter, TNM stage, surgical method, and postoperative immunotherapy.
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Increased applications of quantum dots (QDs) in the biomedical field have aroused attention for their potential toxicological effects. Although numerous studies have been carried out on the toxicity of QDs, their effects on reproductive and development are still unclear. In this study, we systematically evaluated the male reproductive toxicity and developmental toxicity of CdSe/ZnS QDs in BALB/c mice. The male mice were injected intravenously with CdSe/ZnS QDs at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively, and the survival status, biodistribution of QDs in testes, serum sex hormone levels, histopathology, sperm motility and acrosome integrity was measured on Day 1, 7, 14, 28 and 42 after injection. On Day 35 after treatment, male mice were housed with non-exposed female mice, and then offspring number, body weight, organ index and histopathology of major organs, blood routine and biochemical tests of offspring were measured to evaluate the fertility and offspring health. The results showed that CdSe/ZnS QDs could rapidly distribute in the testis, and the fluorescence of QDs could still be detected on Day 42 post-injection. QDs had no adverse effect on the structure of testis and epididymis, but high-dose QDs could induce apoptosis of Leydig cells in testis at an early stage. No significant differences in survival of state, body weight organ index of testis and epididymis, sex hormones levels, sperm quality, sperm acrosome integrity and fertility of male mice were observed in QDs exposed groups. However, the development of offspring was obviously influenced, which was mainly manifested in the slow growth of offspring, changes in organ index of main organs, and the abnormality of liver and kidney function parameters. Our findings revealed that CdSe/ZnS QDs were able to cross the blood-testis barrier (BTB), produce no discernible toxic effects on the male reproductive system, but could affect the healthy growth of future generations to some extent. In view of the broad application prospect of QDs in biomedical fields, our findings might provide insight into the biological safety evaluation of the reproductive health of QDs.
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Puntos Cuánticos/toxicidad , Acrosoma , Animales , Compuestos de Cadmio/química , Compuestos de Cadmio/toxicidad , Epidídimo , Femenino , Fertilidad , Masculino , Ratones , Ratones Endogámicos BALB C , Puntos Cuánticos/química , Reproducción , Compuestos de Selenio/farmacología , Motilidad Espermática , Espermatozoides , Sulfuros/toxicidad , Testículo , Distribución Tisular , Pruebas de Toxicidad , Compuestos de Zinc/toxicidadRESUMEN
Multiple sclerosis (MS) is an autoimmune disease characterized by T cell infiltration and demyelination of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a classical preclinical animal model of MS. In this study, we found that rotating magnetic field (RMF) treatment exerts potential preventive effects on the discovery of EAE, including reducing the severity of the disease and delaying the onset of the disease. The results indicated that RMF (0.2 T, 4 Hz) treatment increases the accumulation of CD4+ cells in the spleen and lymph nodes by downregulating the expression of CCL-2, CCL-3 and CCL-5, but has no significant effect on myelin oligodendrocyte glycoprotein (MOG) specific T cell responses. Simultaneously, RMF treatment adjusted the imbalance between regulatory T (Treg) cell and T helper 1 (Th1) cells or T helper 17 (Th17) cells by increasing the proportion of Treg cells and inhibiting the ratio of Th1 and Th17 cell subsets. These findings suggest that exposure to RMF may improve EAE disease by promoting CD4+ cell accumulation into peripheral lymphoid tissue, improving the imbalance between Treg and Th1/Th17 cells. Therefore, as a mild physical therapy approach, RMF, is likely to be a potential way to alter the development of EAE.
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Linfocitos T CD4-Positivos , Encefalomielitis Autoinmune Experimental , Ganglios Linfáticos/patología , Magnetoterapia/métodos , Esclerosis Múltiple , Bazo/patología , Linfocitos T Reguladores , Células TH1 , Células Th17 , Animales , Recuento de Células/métodos , Citocinas/análisis , Encefalomielitis Autoinmune Experimental/inmunología , Encefalomielitis Autoinmune Experimental/patología , Encefalomielitis Autoinmune Experimental/terapia , Ratones , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/terapia , Glicoproteína Mielina-Oligodendrócito/inmunología , Resultado del TratamientoRESUMEN
MADS box transcription factors (TFs) are subdivided into type I and II based on phylogenetic analysis. The type II TFs regulate floral organ identity and flowering time, but type I TFs are relatively less characterized. Here, we report the functional characterization of two type I MADS box TFs in rice (Oryza sativa), MADS78 and MADS79 Transcript abundance of both these genes in developing seed peaked at 48 h after fertilization and was suppressed by 96 h after fertilization, corresponding to syncytial and cellularized stages of endosperm development, respectively. Seeds overexpressing MADS78 and MADS 79 exhibited delayed endosperm cellularization, while CRISPR-Cas9-mediated single knockout mutants showed precocious endosperm cellularization. MADS78 and MADS 79 were indispensable for seed development, as a double knockout mutant failed to make viable seeds. Both MADS78 and 79 interacted with MADS89, another type I MADS box, which enhances nuclear localization. The expression analysis of Fie1, a rice FERTILIZATION-INDEPENDENT SEED-POLYCOMB REPRESSOR COMPLEX2 component, in MADS78 and 79 mutants and vice versa established an antithetical relation, suggesting that Fie1 could be involved in negative regulation of MADS78 and MADS 79 Misregulation of MADS78 and MADS 79 perturbed auxin homeostasis and carbon metabolism, as evident by misregulation of genes involved in auxin transport and signaling as well as starch biosynthesis genes causing structural abnormalities in starch granules at maturity. Collectively, we show that MADS78 and MADS 79 are essential regulators of early seed developmental transition and impact both seed size and quality in rice.
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Endospermo/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica/genética , Regulación de la Expresión Génica de las Plantas/genética , Proteínas de Dominio MADS/metabolismo , Oryza/crecimiento & desarrollo , Polen/crecimiento & desarrollo , Semillas/crecimiento & desarrollo , Proteínas de Arabidopsis/genética , Carbono/metabolismo , Núcleo Celular/metabolismo , Endospermo/genética , Endospermo/metabolismo , Perfilación de la Expresión Génica , Técnicas de Inactivación de Genes , Ácidos Indolacéticos/metabolismo , Proteínas de Dominio MADS/genética , Microscopía Electrónica de Rastreo , Oryza/genética , Oryza/metabolismo , Infertilidad Vegetal/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente , Polen/genética , Polen/metabolismo , Proteínas del Grupo Polycomb/metabolismo , RNA-Seq , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Semillas/genética , Semillas/metabolismo , Semillas/ultraestructura , Factores de Transcripción/metabolismo , Regulación hacia ArribaRESUMEN
Current study findings concerning changes in the renin-angiotensin system (RAS) in cases of hyperoxic acute lung injury (HALI) have shown conflicting results. This study aimed to detect the angiotensin II (Ang II) and angiotensin-converting enzyme (ACE) in a rat HALI model. Healthy male Sprague-Dawley rats were randomly assigned into three groups: the control group, HALI group and hyperbaric oxygen preconditioning (HBO2-PC) group. HALI was induced by exposure to pure oxygen at 250 kPa for six hours. In the HBO2-PC group, rats were exposed to oxygen at 250 kPa for 60 minutes twice daily for two consecutive days; HALI was induced at 24 hours after the last oxygen exposure.=After HALI, the lung, spleen and liver were harvested for HE staining and pathological examination. At one hour and 18 hours after HALI, the blood, liver, lung and spleen were collected for the detection of Ang II and ACE contents by enzyme-linked immunosorbent assay. Pathological examination showed the lung was significantly damaged and characteristics of HALI were observed, but there were no significant pathological changes in the liver and spleen. After HALI, Ang II and ACE contents of different tissues increased progressively over time, but the HBO2-PC group showed reductions in the Ang II and ACE contents to a certain extent, especially at 18 hours after injury. These findings suggest prolonged hyperoxia exposure may activate the RAS, which may be associated with the pathogenesis of HALI. HBO2-PC has a limited capability to inhibit RAS activation.
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Angiotensina II/análisis , Hiperoxia/metabolismo , Hígado/química , Pulmón/química , Oxígeno/efectos adversos , Peptidil-Dipeptidasa A/análisis , Sistema Renina-Angiotensina , Bazo/química , Lesión Pulmonar Aguda , Angiotensina II/sangre , Animales , Ensayo de Inmunoadsorción Enzimática , Oxigenoterapia Hiperbárica , Hiperoxia/complicaciones , Pulmón/patología , Masculino , Peptidil-Dipeptidasa A/sangre , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Factores de TiempoRESUMEN
Targeted drug decisions in metastatic renal cell carcinoma are exclusively made on the basis of clinical criteria. We investigated whether these biomarkers (HIF-1α, HIF-2α, CAIX, VEGF, VEGFR1, VEGFR2, VEGFR3, PDGFB, PDGFRA, PDGFRB, CD31, CD44, bcl-xL, KIT, p21, CXCR4, PTEN, (CSF)-1R, RET, and FLT-3) can predictive the different effects between sunitinib and sorafenib treatments and are available to guide targeted drug selection. We enrolled all patients who underwent nephrectomy with postoperative sunitinib- or sorafenib-treatment at our institution from 2007 to 2012. Immunohistochemical approach was applied to assess the potential differential effects of immunostainings between sunitinib- and sorafenib-treated groups. We found that patients with high HIF-2α, CD31 expression showed greater relative PFS and OS benefit and patients with high CAIX expression presented greater relative OS benefit from sunitinib than from sorafenib, patients with high VEGFR1 or PDGFRB expression levels exhibited worse relative PFS benefit from sunitinib than from sorafenib. Namely high HIF-2α, CD31, and CAIX expression levels along with low VEGFR1 and PDGFRB expression levels improved the benefit of sunitinib treatment compared with sorafenib treatment. These results can identify whether patients can benefit more from sunitinib or sorafenib for drug selection guidance, eventually with precision medicine.
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Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/análisis , Carcinoma de Células Renales/tratamiento farmacológico , Indoles/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Pirroles/uso terapéutico , Adulto , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Biomarcadores de Tumor/metabolismo , Anhidrasa Carbónica IX/metabolismo , Carcinoma de Células Renales/patología , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Nefrectomía , Niacinamida/uso terapéutico , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Pronóstico , Estudios Prospectivos , Receptor beta de Factor de Crecimiento Derivado de Plaquetas/metabolismo , Sorafenib , Sunitinib , Análisis de Matrices Tisulares , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Edible berries have a broad spectrum of biomedical functions, including improving immune responses and reducing risk for chronic diseases. In this study, the anti-inflammatory activities of crude extracts (CEs), anthocyanin-rich fractions (ARFs), and des-anthocyanin fractions (DAFs) from seven berries were evaluated based on their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)/IFN-γ-activated RAW264.7 macrophages. ARFs from red raspberries (RR-ARFs) exhibited the highest efficiency in suppressing NO synthesis. The anti-inflammatory properties were also demonstrated by reducing the expression levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1 beta (IL-1ß) and IL-6 in RAW264.7 cells. The luciferase reporter assay demonstrated that the activities of NF-κB and AP-1 signaling pathways were significantly suppressed by RR-ARFs. Further studies showed that RR-ARFs decreased the phosphorylation of IKK, IκBα, p65 and JNK and the nuclear translocation of p65 in LPS/IFN-γ-stimulated RAW264.7 cells. In a mouse colitis model, dextran sulfate sodium (DSS)-induced weight loss and histological damage were significantly ameliorated by RR-ARFs treatment. Taken together, our results indicate that RR-ARFs attenuate inflammation both in vitro and in vivo primarily by inhibiting the activation of NF-κB and MAPKs. The anti-inflammatory of RR-ARFs could be harnessed and applied in animal agriculture, drug and food industries.
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Antocianinas/farmacología , Antiinflamatorios/farmacología , Colitis/inmunología , Extractos Vegetales/farmacología , Rubus/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Colitis/tratamiento farmacológico , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Sulfato de Dextran , Frutas/química , Expresión Génica , Interferón gamma/fisiología , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolisacáridos/farmacología , MAP Quinasa Quinasa 4/metabolismo , Ratones Endogámicos BALB C , Morus/química , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismoRESUMEN
Oxygen therapy is one of the most widely used clinical interventions to counteract insufficient pulmonary oxygen delivery in patients with severe lung injury. However, prolonged exposure to hyperoxia at elevated partial pressure leads to inflammation and acute lung injury. The population at risk for this condition has markedly increased with the advent of efficient systems for delivery of high concentrations of oxygen in hospitals. Thus, the therapy of hyperoxia-induced lung injury has been a focus in studies of pediatrics and pulmonary medicine. In this paper, we briefly summarized the advances in the therapies of hyperoxia-induced lung injury on the basis of its pathogenesis. We hope our summary will help provide evidence for further investigation of therapeutic measures for hyperoxia-induced lung injury.
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Lesión Pulmonar Aguda/terapia , Oxigenoterapia Hiperbárica/efectos adversos , Modelos Animales , Terapia por Inhalación de Oxígeno/efectos adversos , Lesión Pulmonar Aguda/etiología , Animales , Estrés Oxidativo , Terapia por Inhalación de Oxígeno/métodos , Presión ParcialRESUMEN
OBJECTIVE: Hyperbaric oxygen (HBO) preconditioning (HBO-PC) has been testified to have protective effects on spinal cord injury (SCI). However, the mechanisms remain enigmatic. The present study aimed to explore the effects of HBO-PC on primary rat spinal neurons against oxidative injury and oxygen-glucose deprivation (OGD) and the relationship with heat shock proteins (HSPs). METHODS: Primary rat spinal neurons after 7 days of culture were used in this study. HSPs were detected in rat spinal neurons following a single exposure to HBO at different time points by Western blot. Using lactate dehydrogenase release assay and cell counting kit-8 assay, the injuries induced by hydrogen peroxide (H2O2) insult or OGD were determined and compared among neurons treated with HBO-PC with or without HSP inhibitors. RESULTS: The results of Western blot showed that HSP27, HSP70 and HSP90 have a slight but not significant increase in primary neurons following HBO exposure. However, HSP32 expression significantly increased and reached highest at 12 h following HBO exposure. HBO-PC significantly increased the cell viability and decreased the medium lactate dehydrogenase content in cultures treated with H2O2 or OGD. Pretreatment with zinc protoporphyrin IX, a specific inhibitor of HSP32, significantly blocked the protective effects of HBO-PC. CONCLUSIONS: These results suggest that HBO-PC could protect rat spinal neurons in vitro against oxidative injury and OGD mostly by up-regulating of HSP32 expression.
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Glucosa/deficiencia , Hemo Oxigenasa (Desciclizante)/metabolismo , Oxigenoterapia Hiperbárica , Neuronas/metabolismo , Estrés Oxidativo/efectos de los fármacos , Oxígeno/farmacología , Columna Vertebral/patología , Regulación hacia Arriba/efectos de los fármacos , Animales , Células Cultivadas , Hipoxia/patología , Neuronas/efectos de los fármacos , Ratas , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/patología , Columna Vertebral/efectos de los fármacos , Factores de TiempoRESUMEN
Hyperbaric oxygen therapy is one of the most widely used clinical interventions to counteract insufficient pulmonary oxygen delivery in patients with severe lung injury. However, prolonged exposure to hyperoxia leads to inflammation and acute lung injury. This study aimed to investigate the protective effect of hydrogen sulfide on hyperbaric hyperoxia-induced lung injury. Rats were intraperitoneally treated with sodium hydrosulphide (NaHS) at 28 µmol/kg immediately before hyperoxia exposure and then exposed to pure oxygen at 2.5 atmospheres absolute (atm abs) with continuous ventilation for six hours, Immediately after hyperoxia exposure, rats were sacrificed via anesthesia. The bronchoalveolar lavage fluid (BALF) was harvested for the detection of protein concentration and IL-1 content, and the lungs were collected for HE staining, TUNEL staining and detection of wet/dry weight ratio. Our results showed hyperbaric hyperoixa exposure could significantly damage the lung (HE staining), increase the protein and IL-13 in the BALF, elevate the wet/dry Weight ratio and raise the TUNEL positive cells. However, pre-treatment with hydrogen sulfide improved the lung morphology, reduced the TUNEL positive cells and attenuated the lung inflammation (reduction in IL-13 of BALF and HE staining). Taken together, our findings indicate that hydrogen sulfide pretreatment may exert protective effects on hyperbaric hyperoxia-induced lung injury.
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Lesión Pulmonar Aguda/prevención & control , Gasotransmisores/uso terapéutico , Sulfuro de Hidrógeno/uso terapéutico , Oxigenoterapia Hiperbárica/efectos adversos , Lesión Pulmonar Aguda/etiología , Animales , Antracenos , Líquido del Lavado Bronquioalveolar/química , Etiquetado Corte-Fin in Situ , Inyecciones Intraperitoneales , Interleucina-1beta/análisis , Pulmón/efectos de los fármacos , Pulmón/patología , Masculino , Proteínas/análisis , Ratas Sprague-Dawley , Sulfuros/farmacologíaRESUMEN
Decompression sickness (DCS) is a major concern in diving and space walk. Hyperbaric oxygen (HBO) preconditioning has been proved to enhance tolerance to DCS via nitric oxide. Heat-shock protein (HSP) 70 was also found to have protective effects against DCS. We hypothesized that the beneficial effects of HBO preconditioning on DCS was related to levels of elevated HSP70. HSPs (70, 27 and 90) expressed in tissues of spinal cord and lung in rats was detected at different time points following HBO exposure by Western blot. HSP27 and HSP90 showed a slight but not significant increase after HBO. HSP70 increased and reached highest at 18 h following exposure before decreasing. Then rats were exposed to HBO and subjected to simulated air dive and rapid decompression to induce DCS 18 h after HBO. The severity of DCS, along with levels of HSP70 expression, as well as the extent of oxidative and apoptotic parameters in the lung and spinal cord were compared among different groups of rats pretreated with HBO, HBO plus NG-nitro-l-arginine-methyl ester (l-NAME), HBO plus quercetin or normobaric air. HBO preconditioning significantly reduced the morbidity of DCS (from 66.7% to 36.7%), reduced levels of oxidation (malondialdehyde, 8-hydroxyguanine and hydrogen peroxide) and apoptosis (caspase-3 and -9 activities and the number of apoptotic cells). l-NAME or quercetin eliminated most of the beneficial effects of HBO on DCS, and counteracted the stimulation of HSP70 by HBO. Bubbles in pulmonary artery were detected using ultrasound imaging to observe the possible effect of HBO preconditioning on DCS bubble formation. The amounts of bubbles in rats pretreated with HBO or air showed no difference. These results suggest that HSP70 was involved in the beneficial effects of HBO on DCS in rats, suspected be by the antioxidation and antiapoptosis effects.
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Enfermedad de Descompresión/patología , Enfermedad de Descompresión/fisiopatología , Proteínas HSP70 de Choque Térmico/metabolismo , Oxigenoterapia Hiperbárica , Animales , Western Blotting , Perfilación de la Expresión Génica , Pulmón/química , Pulmón/patología , Masculino , Ratas , Ratas Sprague-Dawley , Índice de Severidad de la Enfermedad , Médula Espinal/química , Médula Espinal/patologíaRESUMEN
This study was undertaken to investigate the effect of edaravone inhalation on inflammasome activation in a rat hyperoxia-induced lung injury (HILI) model. Sprague Dawley rats (n = 61) were randomly assigned into three groups: Control group, HILI group and Edaravone (Eda) group. Rats in the Control group breathed room air, but those in the HILI group and Eda group were exposed to pure oxygen at 2.5 atmospheres absolute (atm abs) for six hours. Immediately after HILI, rats in the Eda group received inhalation of aerosol edaravone at 0.5 mg/ml for 30 minutes. Twenty-four hours later, rats were sacrificed. The bronchoalveolar lavage fluid (BALF) and lungs were obtained for detection of oxidative stress, IL-1beta, IL-18 and caspase-1; the lungs were collected for HE staining and TUNEL staining. The pathological features of the lungs of rats in the Eda group were significantly improved when compared with the HILI group, accompanied by reduction in apoptotic cells. In addition, in the Eda group, the malonyldialdehyde (MDA) was reduced and total antioxidant capacity (T-AOC) was increased significantly in the lung and BALF when compared with the HILI group (P < 0.05 for both). Moreover, the contents of IL-1beta, IL-18 and caspase-1 in the lung and BALF, downstream factors of inflammasome, were also dramatically lower in the Eda group than in the HILI group (P < 0.05 for all). These findings suggest that edaravone may inhibit inflammasome activation due to its anti-oxidative capacity exerting a protective effect on HILI.
Asunto(s)
Antipirina/análogos & derivados , Depuradores de Radicales Libres/administración & dosificación , Hiperoxia/complicaciones , Lesión Pulmonar/metabolismo , Especies Reactivas de Oxígeno , Receptores Citoplasmáticos y Nucleares/efectos de los fármacos , Animales , Antioxidantes/metabolismo , Antipirina/administración & dosificación , Apoptosis , Agua Corporal , Líquido del Lavado Bronquioalveolar/química , Proteínas Portadoras , Caspasa 1/análisis , Modelos Animales de Enfermedad , Edaravona , Oxigenoterapia Hiperbárica/efectos adversos , Interleucina-18/análisis , Interleucina-1beta/análisis , Pulmón/química , Pulmón/patología , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Lesión Pulmonar/prevención & control , Masculino , Malondialdehído/análisis , Proteína con Dominio Pirina 3 de la Familia NLR , Estrés Oxidativo , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Receptores Citoplasmáticos y Nucleares/metabolismoRESUMEN
Divers are at risk of decompression sickness (DCS) when the ambient pressure decrease exceeds a critical threshold. Hyperbaric oxygen (HBO2) preconditioning has been used to prevent various injuries, but the protective effect on DCS has not been well explored. To investigate the prophylactic effect of HBO2 on DCS, rats were pretreated with HBO2 (250 kPa-60 minutes) (all the pressures described here are absolute pressure) for 18 hours before a simulated air dive (700 kPa-100 minutes) with fast decompression to the surface at the rate of 200 kPa/min (n=33). During the following 30 minutes, the rats walked in a 3 m/minute rotating cage and were monitored for signs of DCS. The control rats were pretreated with normobaric air (n=30), normoxic hyperbaric nitrox (250 kPa, 8.4% O2) (n=13), or N(G)-nitro-L-arginine methyl ester (L-NAME) 30 minutes before HBO2 exposure (n=13). Nitric oxide (NO) levels were recorded immediately and 18 hours after HBO2 exposure in the brain and spinal cord. The incidence of DCS in rats pretreated with HBO2 was 30.3%, which was significantly lower than those treated with normobaric air (63.3%) (p<0.05) or hyperbaric nitrox (61.5%) (p<0.05). The onset time of DCS of the rats pretreated with HBO2 was significantly delayed compared with those treated with air (p<0.05). L-NAME nullified the HBO2 preconditioning effect. HBO2 increased NO level in the rat brain and spinal cord right after exposure; this effect was inhibited by L-NAME. Taken together, HBO2 preconditioning reduced the incidence of DCS in rats, and NO was involved in the prophylactic effect.
Asunto(s)
Enfermedad de Descompresión/prevención & control , Oxigenoterapia Hiperbárica/métodos , Óxido Nítrico/metabolismo , Animales , Encéfalo/metabolismo , Enfermedad de Descompresión/metabolismo , Inhibidores Enzimáticos/administración & dosificación , Masculino , Actividad Motora/fisiología , NG-Nitroarginina Metil Éster/administración & dosificación , Óxido Nítrico/análisis , Nitrógeno/administración & dosificación , Oxígeno/administración & dosificación , Ratas , Ratas Sprague-Dawley , Médula Espinal/metabolismo , Factores de TiempoRESUMEN
BACKGROUND: Repetitive hyperbaric oxygen (HBO) exposures as preconditioning methods produce ischemic tolerance, but may increase the risk of convulsions in patients. The purpose of this study was to investigate the mechanisms in increased sensitivity to convulsions and the role of nitric oxide (NO) and its synthases after repetitive HBO exposures. METHODS: Mice were randomly assigned into three groups: HBO group, hyperbaric air (HBA) group and normobaric air (NBA) group. Mice in HBO or HBA group were exposed to hyperbaric oxygen or hyperbaric air respectively for 60 min twice daily for 3 consecutive days (2.5 atmosphere absolute [ATA]). 24 h after the last exposure, mice were exposed to HBO (100% O2, 6 ATA). The latency of convulsions was recorded. In addition, the levels of NO, NADPH-diaphorase, mRNA and protein expressions of NOS isoforms in hypothalamus and hippocampus were determined. RESULTS: Latency to seizures was significantly shortened in mice after six HBO pre-exposures. The level of NO in hypothalamus in HBO group was increased. The number of NADPH-d positive cells and the levels of protein and mRNA of eNOS and nNOS in hypothalamus and hippocampus were increased. CONCLUSION: After repeated HBO exposures, elevated NO may enhance the sensitivity to convulsions and this may lead to seizures during the subsequent oxygen exposures. Prevention of seizures is needed when HBO is used as preconditioning method.
Asunto(s)
Encéfalo/enzimología , Oxigenoterapia Hiperbárica/efectos adversos , Óxido Nítrico Sintasa de Tipo III/metabolismo , Óxido Nítrico Sintasa de Tipo I/metabolismo , Convulsiones/enzimología , Convulsiones/etiología , Animales , Encéfalo/fisiopatología , Química Encefálica/fisiología , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Hipocampo/enzimología , Hipotálamo/enzimología , Masculino , Ratones , NADPH Deshidrogenasa/metabolismo , Óxido Nítrico/biosíntesis , Óxido Nítrico Sintasa de Tipo I/genética , Óxido Nítrico Sintasa de Tipo III/genética , Oxígeno/efectos adversos , ARN Mensajero/metabolismo , Convulsiones/fisiopatología , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiologíaRESUMEN
OBJECTIVE: To observe the therapeutic effect of transcutaneous point electric stimulation on periarthritis of shoulder at different stages and compare with electroacupuncture. METHODS: Three hundred and sixty cases of periarthritis of shoulder at different stages were divided into a treatment group (n=186) treated with transcutaneous point electric stimulation, and a control group (n=174) treated with electroacupuncture. Same acupoints were selected in the two groups. RESULTS: The total effective rate of transcutaneous point electric stimulation was 96.6% at the adhesion prophase and 96.9% at the adhesive stage, but electroacupuncture stimulation was 93.5% and 97.9%, respectively, with no significant differences between the two groups; transcutaneous point electric stimulation not only could relieve pain, but also significantly improve dysfunction of shoulder joints at the adhesive stage. CONCLUSION: Transcutaneous point electric stimulation is an effective and convenient therapy for periarthritis of shoulder.