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1.
Acta Neurochir Suppl ; 127: 47-54, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31407062

RESUMO

BACKGROUND: Previously studies have shown that Nox2 and Nox4, as members of nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase, Nox), participate in brain damage caused by ischemia-reperfusion (I/R). The aim of this study is to investigate the effects of specific chemical inhibitors of Nox2 and Nox4 on cerebral I/R-induced brain injury in rats. METHODS: At 0.5 h before MCAO surgery, the rats were pretreated with vehicle, Nox2 inhibitor (gp91ds-tat), and Nox4 inhibitor (GKT137831), respectively. After reperfusion for 24 h, the infarct sizes of brain tissues in rats in various groups are determined. The penumbra (ischemic) tissues are collected to measure ROS levels, neuronal apoptosis, and degeneration, as well as the integrity of the blood-brain barrier (BBB) in brain tissues of rats. RESULTS: gp91ds-tat and GKT137831 pretreatment significantly reduced the infarct sizes in brain tissues of rats, effectively suppressed I/R-induced increase in ROS levels, neuronal apoptosis and degeneration, and obviously alleviated BBB damage. CONCLUSION: Under cerebral I/R conditions, Nox2 inhibitor (gp91ds-tat) and Nox4 inhibitor (GKT137831) can effectively play a protective role in the brain tissues of rats.


Assuntos
Lesões Encefálicas , Isquemia Encefálica , NADPH Oxidase 2 , NADPH Oxidase 4 , Traumatismo por Reperfusão , Animais , Apoptose/efeitos dos fármacos , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , NADPH Oxidase 2/antagonistas & inibidores , NADPH Oxidase 2/metabolismo , NADPH Oxidase 4/antagonistas & inibidores , NADPH Oxidase 4/metabolismo , NADPH Oxidases , Ratos , Espécies Reativas de Oxigênio , Traumatismo por Reperfusão/metabolismo
2.
Medicine (Baltimore) ; 98(42): e17591, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626131

RESUMO

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCII) is a common complication of spinal surgery as well as thoracic and abdominal surgery. Acute cytotoxic edema is the key pathogenic alteration. Therefore, avoiding or decreasing cellular edema has become the major target for SCII treatment. METHODS: The antiedema activity of ginsenoside Rb1 on aquaporin (AQP) 4, nerve growth factor (NGF), and brain-derived neurotrophic factor expression was detected by western blot and real-time polymerase chain reaction under conditions of oxygen-glucose deprivation/reoxygenation (OGD/R) in a rat astrocyte model in vitro. In addition, the cellular membrane permeability of AQP4 overexpressing cells or AQP4 small interfering RNA-transfected cells was detected. RESULTS: Ginsenoside Rb1 significantly prevented OGD/R-induced AQP4 downregulation in rat astrocytes. In addition, ginsenoside Rb1 treatment or AQP4 overexpression in rat astrocytes significantly attenuated the OGD/R-induced increase of cellular membrane permeability. Moreover, ginsenoside Rb1 obviously prevented the OGD/R-induced decrease of NGF and BDNT expression in rat astrocytes. CONCLUSION: These findings demonstrate that ginsenoside Rb1 can relieve spinal cord edema and improve neurological function by increasing AQP4 expression.


Assuntos
Aquaporina 4/genética , Astrócitos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Ginsenosídeos/farmacologia , Glucose/metabolismo , Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Animais , Animais Recém-Nascidos , Aquaporina 4/biossíntese , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Western Blotting , Células Cultivadas , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , RNA/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/metabolismo , Medula Espinal/patologia
3.
Rev Assoc Med Bras (1992) ; 65(9): 1193-1200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618337

RESUMO

OBJECTIVES: This study was conducted to reveal the possible protective effects of ticagrelor and enoxaparin pretreatment against ischemia-reperfusion (IR)-induced injury on the lung tissue of a rat model. METHODS: Wistar albino rats were randomly divided into 4 groups as follows: group-1 (control-sham), group-2 (control-saline+IR), group-3 (ticagrelor+IR), group-4 (enoxaparin+IR). Before the ischemic period, saline, ticagrelor, and enoxaparin were administered to the 2nd-4th groups, respectively. In these groups, IR injury was induced by clamping the aorta infrarenally for 2 h, followed by 4 h of reperfusion except group-1. After the rats were euthanized, the lungs were processed for histological examinations. Paraffin sections were stained with Haematoxylin&Eosin (H&E) for light microscopic observation. Apoptosis was evaluated by caspase-3 immunoreactivity. Data were statistically analyzed using the SPSS software. RESULTS: In the lung sections stained with H&E, a normal histological structure was observed in group-1, whereas disorganized epithelial cells, hemorrhage, and inflammatory cell infiltration were seen in the alveolar wall in group-2. The histologic structure of the treatment groups was better than that of group-2. Caspase-3(+) apoptotic cells were noticeable in sections of group-2 and were lower in the treatment groups. In group-4, caspase-3 immunostaining was lower than in group-3. In group-2, apoptotic cells were significantly higher than in the other groups (p<0.001). CONCLUSION: Based on the histological results, we suggested that both therapies ameliorated the detrimental effects of IR. Caspase-3 immunohistochemistry results also revealed that pre-treatment with enoxaparin gave better results in an IR-induced rat injury model. In further studies, other parameters such as ROS and inflammatory gene expressions should be evaluated for accurate results.


Assuntos
Aorta Abdominal/cirurgia , Enoxaparina/farmacologia , Pulmão/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Ticagrelor/farmacologia , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Modelos Animais de Doenças , Pulmão/patologia , Lesão Pulmonar/prevenção & controle , Masculino , Distribuição Aleatória , Ratos Wistar , Traumatismo por Reperfusão/patologia
4.
J Biol Regul Homeost Agents ; 33(5): 1405-1413, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31659953

RESUMO

Lung ischemia-reperfusion injury (LIRI) is a common and severe clinical complication. As the injury occurs, the pulmonary afferent nerves play an important role in regulating respiratory functions under pathophysiological conditions. The purpose of this study was to examine expression of proteinaseactivated receptor-2 (PAR2) and transient receptor potential A1 (TRPA1) in pulmonary vagal afferent nerves of LIRI and further to determine molecular mediators linking activation of PAR2 and TRPA1. A rat model of LIRI was used. Enzyme-linked immunosorbent assay (ELISA) and Western blot analysis were employed to examine pro-inflammatory cytokines (PICs, i.e., IL-1ß, IL-6 and TNF-α), and the protein levels of PIC receptors, PAR2, TRPA1, and intracellular signals. In the results, IL-1ß, IL-6 and TNF-α along with their receptors were amplified in afferent nerves of LIRI rats as compared with control rats. Sensory PAR2 and TRPA1 were also upregulated by LIRI. Blocking PAR2 by infusion of FSLLRY-NH2 attenuated upregulation of TRPA1 via intracellular signals, namely p38-MAPK and JNK. Moreover, blocking individual PIC receptor attenuated PAR2 and TRPA1 in pulmonary vagal afferent nerves. Our data showed specific signaling pathways leading LIRI to activation of PIC signal and activation of PAR2 and TRPA1 in pulmonary vagal afferent nerves via intracellular mediators. Targeting one or more of these signaling molecules may present opportunities to improve the abnormalities in vagal afferent nerve-mediated respiratory functions observed as LIRI occurs.


Assuntos
Pulmão/patologia , Receptor PAR-2/metabolismo , Traumatismo por Reperfusão , Canal de Cátion TRPA1/metabolismo , Nervo Vago/metabolismo , Animais , Ratos
5.
Life Sci ; 236: 116921, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610196

RESUMO

AIMS: To assess the role of glycogen synthase kinase-3ß (GSK3ß) and ß-catenin in the protection of ischemic injury by dexmedetomidine (Dex). MAIN METHODS: Adult male Sprague-Dawley rats were subjected to (middle cerebral artery occlusion, MCAO) for 2 h followed by reperfusion and Dex was administered 30min before MCAO. The neurological deficit score, cerebral infarct size and neuron survival were evaluated at 24 h after reperfusion. The expression of pAKT, pGSK3ß and ß-catenin in the ischemic penumbra was assayed by Western blot at 2 h after reperfusion. KEY FINDINGS: We found that the Dex-induced increment of neuron survival in the ischemic penumbra was diminished by the PI3K inhibitor LY294002 and the ß-catenin inhibitor XAV939, respectively. The increasing expression of pAKT, pGSK3ß and ß-catenin induced by Dex was markedly inhibited by LY294002. And the increasing expression of ß-catenin in nuclei induced by Dex was markedly inhibited by XAV939. At the same time, the GSK3ß inhibitor SB216763 also caused an increment of neuron survival and an increasing expression of pGSK3ß and ß-catenin in the ischemic penumbra. SIGNIFICANCE: Our data suggested that treatment with Dex reduced cerebral injury in rats exposed to cerebral ischemia-reperfusion (I/R) by the activation of the PI3K/AKT/GSK3ß pathways as well the activation of downstream Wnt/ß-catenin pathway. And the Wnt/ß-catenin pathway may play an important role in the protection against cerebral ischemia/reperfusion injury in rats.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacologia , Dexmedetomidina/farmacologia , Infarto da Artéria Cerebral Média/prevenção & controle , Traumatismo por Reperfusão/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Animais , Apoptose , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Masculino , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Proteínas Wnt/genética , beta Catenina/genética
6.
Acta Cir Bras ; 34(8): e201900805, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618405

RESUMO

PURPOSE: To investigate the effect of sevoflurane preconditioning on ischemia/reperfusion (I/R)-induced pulmonary/hepatic injury. METHODS: Fifty-one Wistar rats were randomly grouped into sham, I/R, and sevoflurane groups. After reperfusion, the structural change of the lung was measured by Smith score, the wet and dry weights (W/D) were determined, malondialdehyde (MDA) myeloperoxidase (MPO) content was determined colorimetrically and by fluorescence, respectively, and matrix metalloprotein-9 (MMP-9) mRNA was quantified by RT-PCR. Biopsy and morphological analyses were performed on liver tissue, activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were determined, and tumor necrosis factor-alpha (TNF-α) level was determined. RESULTS: The sham group showed no changes in tissue structure. Structural lesions in the sevoflurane and I/R groups were mild and severe, respectively. Smith score, W/D, MDA, MPO, and MMP mRNA showed the same trend, and were increased in the I/R group and recovered in the sevoflurane group, compared with the sham group (both P<0.05). AST and ALT were significantly increased compared to the sham group (AST: 655±52.06 vs . 29±9.30 U/L; ALT: 693±75.56 vs . 37±6.71 U/L; P<0.05). In the sevoflurane group, AST and ALT levels were significantly decreased (464±47.71 and 516±78.84 U/L; P<0.001). TNF-α presented similar results. CONCLUSION: The protection of lung and liver by sevoflurane may be mediated by inhibited leukocyte recruitment and MMP-9 secretion.


Assuntos
Anestésicos Inalatórios/uso terapêutico , Precondicionamento Isquêmico/métodos , Fígado/irrigação sanguínea , Pulmão/irrigação sanguínea , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/uso terapêutico , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Isquemia/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Malondialdeído/análise , Peroxidase/análise , Ratos , Ratos Wistar , Traumatismo por Reperfusão/tratamento farmacológico , Fator de Necrose Tumoral alfa/sangue
7.
Acta Cir Bras ; 34(8): e201900806, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31618406

RESUMO

PURPOSE: To assess Cyclosporine A (CsA) therapy at an intraperitoneal dose of 15 mg.kg -1 in a rodent model of non-septic renal ischemia. METHODS: Twenty male Wistar rats were randomized to receive CsA therapy or none therapy before undergoing 30 minutes of renal ischemia followed by reperfusion. Additionally, 10 rats were randomized to undergo the same surgical procedure of the aforementioned animals with neither ischemia nor CsA therapy. Twelve hours after kidney ischemia, the left kidneys were evaluated for histological injury according to Park's criteria. Serum creatinine (Cr), urea nitrogen (Ur) and sodium levels were obtained at different times of the experimental protocol. RESULTS: Rodents in the CsA group showed negative results (p<0.05) in serum variables (Cr: 0.41±0.05mg/dL vs . 4.17±1.25mg/dL; Ur: 40.90±3.98mg/dL vs . 187.70±22.93mg/dL) even the non CsA or control group (Cr: 0.35±0.07mg/dL vs . 3.80±1.20mg/dL; Ur: 40.10±4.70mg/dL vs . 184.50±49.80mg/dL). The negative results were also verified in histological evaluation, CsA group had 50% in the very severe grade of lesion, 10% in the severe and 40% in the moderate to severe whereas the control group had 90% in the very severe grade. CONCLUSION: CsA was incapable of preventing the deleterious effects of ischemia-reperfusion injury in rat kidneys.


Assuntos
Ciclosporina/farmacologia , Imunossupressores/farmacocinética , Rim/irrigação sanguínea , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Creatinina/sangue , Modelos Animais de Doenças , Isquemia/prevenção & controle , Rim/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Traumatismo por Reperfusão/patologia , Sódio/sangue , Ureia/sangue
8.
DNA Cell Biol ; 38(10): 1025-1029, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31532239

RESUMO

Neutrophil trafficking into damaged or infected tissues is essential for the initiation of inflammation, clearance of pathogens and damaged cells, and ultimately tissue repair. Neutrophil recruitment is highly dependent on the stepwise induction of adhesion molecules and promigratory chemokines and cytokines. A number of studies in animal models have shown the efficacy of cannabinoid receptor 2 (CB2) agonists in limiting inflammation in a range of preclinical models of inflammation, including colitis, atherosclerosis, multiple sclerosis, and ischemia-reperfusion injury. Recent work in preclinical models of inflammation raises two questions: by what mechanisms do CB2 agonists provide anti-inflammatory effects during acute inflammation and what challenges exist in the translation of CB2 modulating therapeutics into the clinic.


Assuntos
Aterosclerose/genética , Colite/genética , Esclerose Múltipla/genética , Neutrófilos/metabolismo , Receptor CB2 de Canabinoide/genética , Traumatismo por Reperfusão/genética , Animais , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Aterosclerose/patologia , Agonistas de Receptores de Canabinoides/uso terapêutico , Antagonistas de Receptores de Canabinoides/uso terapêutico , Colite/tratamento farmacológico , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Citocinas/farmacologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Inflamação , Ligantes , Camundongos , Camundongos Knockout , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , Infiltração de Neutrófilos , Neutrófilos/efeitos dos fármacos , Neutrófilos/patologia , Receptor CB2 de Canabinoide/agonistas , Receptor CB2 de Canabinoide/antagonistas & inibidores , Receptor CB2 de Canabinoide/deficiência , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia
9.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(8): 944-949, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31511215

RESUMO

OBJECTIVE: To verify whether dexmedetomidine hydrochloride (Dex) alleviates renal ischemia-reperfusion (IR) injury in diabetic rats by increasing the expression of hypoxia inducible factor-1α (HIF-1α). METHODS: A rat model of type 2 diabetes mellitus was established by high-fat diet and streptozotocin injection. The rats were subjected to daily intragastric administration of 0.05 mg/kg digoxin for 7 consecutive days and intraperitoneal injection of Dex 2 h before renal IR injury induced by ligation of the bilateral renal arteries for 60 min followed by reperfusion for 120 min. After reperfusion, blood samples were taken for detection of serum creatinine (Scr) and urea nitrogen (BUN) levels. Western blotting was used to detect the expression of HIF-1α, cleaved caspase-3, Bcl-2, and Bax in the renal tissues; the expression of the HIF-1α, p-eNOS, and eNOS were detected using ELISA. The percentage of apoptotic glomerular cells was assessed using TUNEL assay. RESULTS: The levels of Scr, BUN, HIF-1α, p-eNOS, and eNOS and the percentage of apoptotic cells in both normal and diabetic rats increased significantly after renal IR injury (P < 0.05). The expressions of Scr, BUN, p-eNOS, and eNOS decreased while HIF-1α expression increased significantly in Dex-treated rats with renal IR injury (P < 0.05). Compared with the non-diabetic rats, the diabetic rats showed more obvious increase in the expressions of Scr, BUN, p-eNOS, and eNOS following renal IR injury. In the diabetic rats with renal IR injury, Dex treatment prior to the injury significantly lowered the expressions of Scr, BUN, p-eNOS, eNOS, cleaved caspase-3, and Bax, decreased the percentage of apoptotic cells, and increased the levels of HIF-1a and Bcl-2 (P < 0.05). Digoxin treatment significantly antagonized the effects of Dex in the diabetic rats with renal IR injury by increasing the expressions of cleaved caspase-3 and Bax, promoting glomerular cell apoptosis, and decreasing renal expressions of HIF-1 and Bcl-2 (P < 0.05). CONCLUSIONS: Dex alleviates renal IR injury in diabetic rats probably by inhibiting renal expression of HIF-1α and glomerular cell apoptosis.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Traumatismo por Reperfusão , Animais , Dexmedetomidina , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia , Rim , Ratos , Ratos Sprague-Dawley
10.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(8): 980-986, 2019 Aug 30.
Artigo em Chinês | MEDLINE | ID: mdl-31511220

RESUMO

OBJECTIVE: To investigate the signaling pathways that mediate the protective effects of dexmedetomidine on lung tissue against ischemia-reperfusion (I/R) injury during cardiopulmonary bypass (CPB). METHODS: Forty adult SD rats were randomized into 5 groups, namely I/R group (group A), dexmedetomidine group (group B), sham-operated group (group C), oxypenicillin group (group D), and oxypenicillin + dexmedetomidine group (group E). The arterial blood gas, lung tissue apoptosis rate, protein kinase (Akt), phosphorylated Akt (p-AKT), caspase-3 and caspase-9 were compared among the 5 groups. RESULTS: In groups A, B, D and E, the heart rate (HR), mean arterial pressure (MAP), and oxygenation index (OI) measured before CPB, at opening of the left hilar and at the end of experiment decreased gradually while the respiratory index (RI) increased at the 3 time points. At the end of experiment, HR, MAP, and OI in group B were significantly higher and RI was significantly lower than those in groups A, D and E (P < 0.05). In groups A-E, the pathological scores of the lung tissue at the end of the experiment were 4.89, 1.89, 0, 6.01 and 5.76, respectively, and the cell apoptosis rates in the lung tissue were 6.25%, 3.69%, 1.06%, 8.06% and 7.79%, respectively (P < 0.001). Western blotting showed that the expressions of Akt and p-AKT were the highest and those of caspase-3 and caspase-9 were the lowest in group B among the 5 groups (P < 0.05). CONCLUSIONS: Dexmedetomidine can effectively alleviate lung injury in rats during CPB possibly by targeting caspase-3 and caspase-9 proteins that are related to PI3K/Akt signaling pathway.


Assuntos
Traumatismo por Reperfusão , Animais , Ponte Cardiopulmonar , Dexmedetomidina , Fosfatidilinositol 3-Quinases , Ratos , Ratos Sprague-Dawley
11.
Zhongguo Zhen Jiu ; 39(9): 957-62, 2019 Sep 12.
Artigo em Chinês | MEDLINE | ID: mdl-31544384

RESUMO

OBJECTIVE: To explore the protective effect and apoptosis-related mechanism of electroacupuncture (EA) preconditioning in the rats with cerebral ischemia-reperfusion injury. METHODS: Sixty male SD rats, 3 months old, at SPF grade were randomized into a sham-operation group, an ischemia-reperfusion group and an EA preconditioning group, 20 rats in each one. In the ischemia-reperfusion group and EA preconditioning group, the modified MCAO suture-occlusion method was adopted to exert ischemia for 2 h and reperfusion for 3 h, and thus, the models of focal cerebral ischemia-reperfusion injury were prepared on the right side. In the sham-operation group, the right common carotid artery was separated and no more management was given. In the EA preconditioning group, EA at "Baihui" (GV 20), "Shenshu" (BL 23) and "Sanyinjiao" (SP 6) was provided before modeling, with disperse-dense wave, at 2 Hz/100 Hz, 1 mA in intensity. The stimulation for 15 min was taken as one unit (meaning electric stimulation for 10 min and needle retaining for 5 min without electric stimulation). Such preconditioning was repeated continuously for 4 times, totally for 1 h. The neuroethologic condition was assessed in 3 h of reperfusion in each group. TTC staining method was used to determine the percentage of cerebral infarction zone, TUNEL method was to determine the apoptosis index (AI) in hippocampal neuron and the immunohistochemical method (IHC) was to determine the protein expression of p53 and caspase-3. RESULTS: Compared with the sham-operation group, the neuroethologic score, the percentage of cerebral infarction zone and neuronal AI were all increased obviously in the ischemia-reperfusion group (all P<0.01). Compared with the ischemia-reperfusion group, the neuroethologic score, the percentage of cerebral infarction zone and neuronal AI were all reduced obviously in the EA preconditioning group (all P<0.01). p53's nuclei and caspase-3's cytoplasms were stained. The positive cells of both of them were brown-yellow in color. In the sham-operation group, the structure of the right hippocampal CA3 neurons of rats was clear, with few positive cells. In the ischemia-perfusion group, the positive expressions of p53 and caspase-3 in the right hippocampal CA3 were increased obviously (P<0.01). Compared with the ischemia-reperfusion group, the positive expressions of caspase-3 and p53 in the right hippocampal CA3 were significantly reduced in the EA preconditioning group (P<0.01). CONCLUSION: Electroacupuncture preconditioning relieves ischemic injury in brain tissue of rats probably through inhibiting the expressions of p53 and caspase-3 to resisting neuronal apoptosis.


Assuntos
Isquemia Encefálica , Caspase 3 , Eletroacupuntura , Traumatismo por Reperfusão , Proteína Supressora de Tumor p53 , Pontos de Acupuntura , Animais , Caspase 3/fisiologia , Hipocampo , Humanos , Masculino , Neurônios , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Proteína Supressora de Tumor p53/fisiologia
12.
Br J Anaesth ; 123(5): 584-591, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31521337

RESUMO

BACKGROUND: The REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal function after living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation. METHODS: In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor-recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss. RESULTS: There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min-1 (1.73 m)-2 [95% confidence interval, CI: 1.54-7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43-1.43]). CONCLUSIONS: RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia. CLINICAL TRIAL REGISTRATION: ISRCTN30083294.


Assuntos
Precondicionamento Isquêmico/métodos , Transplante de Rim , Traumatismo por Reperfusão/prevenção & controle , Adolescente , Adulto , Idoso , Aloenxertos , Método Duplo-Cego , Europa (Continente) , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/fisiologia , Rim/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Tempo , Resultado do Tratamento , Adulto Jovem
13.
Life Sci ; 235: 116840, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31494171

RESUMO

AIMS: Ovarian ischemia as a consequence of torsion constitutes a gynecologic emergency affecting females during reproductive age. Its management by detorsion results in ovarian ischemia-reperfusion (IR) injury. Thus, a conservative treatment with detorsion is highly recommended. Therefore, we attempted to investigate the effect and underlying mechanisms of angiotensin 1-7 (Ang-(1-7)) treatment against ovarian IR injury. MAIN METHODS: Female rats were included into: Sham group; Ang-(1-7) (300 µg/kg, i.p.) group; ovarian IR groups with and without Ang-(1-7) treatment. We determined ovarian Ang-(1-7), malondialdehyde (MDA) and nitric oxide (NO) in addition to serum total anti-oxidant capacity (TAC) levels. Ovarian gene expressions of angiotensin converting enzyme 2 (ACE2), Mas receptor, tumor necrosis factor alpha (TNF-α) and B-cell leukemia/lymphoma-2 (BCL-2) were estimated. Furthermore, histopathological changes and ovarian expressions of nuclear factor kappa B (NF-κB), inducible and endothelial nitric oxide synthases (iNOS and eNOS) were done. KEY FINDINGS: Treatment of ovarian IR rats with Ang-(1-7) led to marked improvement of ovarian damage through histological examination which was accompanied with marked increase in ovarian Ang-(1-7) level and expressions of ACE2 and Mas receptor, decrease in MDA and NO levels and expressions of NF-kB, iNOS and TNF-α with increase in serum TAC levels and ovarian expressions of eNOS and BCL-2. SIGNIFICANCE: Our results proved the protective effect of Ang-(1-7) against ovarian IR injury in rats and this may be attributed to ACE2/Ang (1-7)/Mas axis which showed anti-oxidant, anti-inflammatory and anti-apoptotic effects. Therefore, Ang-(1-7) can be used in the future for treatment of ovarian IR injury.


Assuntos
Angiotensina I/farmacologia , Ovário/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Antioxidantes/metabolismo , Feminino , Expressão Gênica/efeitos dos fármacos , Malondialdeído/metabolismo , NF-kappa B/biossíntese , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo III/biossíntese , Ovário/lesões , Ovário/metabolismo , Peptidil Dipeptidase A/biossíntese , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Ratos , Receptores Acoplados a Proteínas-G/biossíntese , Soro/metabolismo , Fator de Necrose Tumoral alfa/biossíntese
14.
Acta Cir Bras ; 34(7): e201900707, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31531528

RESUMO

PURPOSE: To evaluate the effects of splenic ischemic preconditioning (sIPC) on oxidative stress induced by hepatic ischemia-reperfusion in rats. METHODS: Fifteen male Wistar rats were equally divided into 3 groups: SHAM, IRI and sIPC. Animals from IRI group were subjected to 45 minutes of partial liver ischemia (70%). In the sIPC group, splenic artery was clamped in 2 cycles of 5 min of ischemia and 5 min of reperfusion (20 min total) prior to hepatic ischemia. SHAM group underwent the same surgical procedures as in the remaining groups, but no liver ischemia or sIPC were induced. After 1h, hepatic and splenic tissue samples were harvested for TBARS, CAT, GPx and GSH-Rd measurement. RESULTS: sIPC treatment significantly decreased both hepatic and splenic levels of TBARS when compared to IRI group (p<0.01). Furthermore, the hepatic and splenic activities of CAT, GPx and GSH- Rd were significantly higher in sIPC group than in IRI group. CONCLUSION: sIPC was able to attenuate hepatic and splenic IRI-induced oxidative stress.


Assuntos
Precondicionamento Isquêmico/métodos , Hepatopatias/prevenção & controle , Fígado/irrigação sanguínea , Estresse Oxidativo/fisiologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Modelos Animais de Doenças , Fígado/fisiologia , Hepatopatias/fisiopatologia , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar , Traumatismo por Reperfusão/fisiopatologia
15.
Zhen Ci Yan Jiu ; 44(9): 649-52, 2019.
Artigo em Chinês | MEDLINE | ID: mdl-31532133

RESUMO

OBJECTIVE: To observe the effect of electroacupuncture (EA) of "Baihui" (GV20) and "Zusanli" (ST36) on the expression of stromal cell derived factor-1α (SDF-1α) and CD34 in ischemic cortex tissue of cerebral ische-mia /reperfusion injury (CI/RI) rats, so as to study its mechanisms underlying improving CI/RI. METHODS: Thirty male SD rats were equally and randomly divided into sham operation, model and EA groups (n=10 rats in each group). The CI/RI model was established by occlusion of the middle cerebral artery for 120 min, followed by reperfusion. EA (40 Hz, 1-2 mA) was applied to GV20 and left ST36 for 20 min, once daily for successive 14 days. The neurological deficit severity was assessed by using Longa's and colleagues' methods. The histopathological changes of the ischemic tissues were observed after H.E. staining and the expression of SDF-1α and CD34 in the ischemic cortex tissues was detected by immunohistochemistry. RESULTS: After modeling, the neurological deficit score, and the numbers of SDF-1α and CD34-positive cells in the ischemic cerebral cortex tissue were significantly increased in the model group (P<0.05). Following EA intervention, the increased neurological deficit score was reversed at the 3rd, 7th and 14th day, and the increased SDF-1α and CD34-positive cells were significantly further up-regulated in the EA group (P<0.05). H.E. staining showed tissue edema, widening of the intercellular space, cavitation-like changes, neuronal shrinkage, nuclear pyknosis with hyperchroma or even disappearance, and aggregation of inflammatory and neurogliocytes in the model group. These situations were relatively milder in the EA group. CONCLUSION: EA of GV20 and ST36 can improve neurological function of CI/RI rats, which may be associated with its effect in up-regulating the expression of SDF-1α and CD34 proteins in the ischemic cerebral cortex tissues.


Assuntos
Isquemia Encefálica , Eletroacupuntura , Traumatismo por Reperfusão , Animais , Quimiocina CXCL12 , Masculino , Ratos , Ratos Sprague-Dawley , Células Estromais
16.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 35(7): 601-605, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31537244

RESUMO

Objective To determine whether regulatory T cells (Tregs) are involved in sevoflurane preconditioning-induced brain protection against cerebral ischemia/reperfusion injury. Methods C57BL/6 mice were preconditioned with sevoflurane and then subjected to the middle cerebral artery occlusion modeling. The brain infarct volume and neurological score were assessed at 48 hours after cerebral reperfusion. Meanwhile, the proportion of Tregs in the spleen was analyzed by flow cytometry. Then, CD25 neutralizing antibody was administrated by intraperitoneal injection, following with the analysis of cerebral ischemia/reperfusion injury and the proportion of Tregs in the spleen after sevoflurane preconditioning. Results Compared with a control group, sevoflurane preconditioning markedly mitigated the cerebral ischemia/reperfusion injury in the mice including the infarct volume and neurological score. In the meantime, sevoflurane preconditioning significantly increased the proportion of Tregs in the spleen at 48 hours after cerebral reperfusion. Compared with the isotype antibody group, the CD25 neutralizing antibody reversed the increase of Tregs induced by sevoflurane preconditioning at 48 hours after reperfusion, which was also associated with the reversal of sevoflurane preconditioning-induced protectetion against cerebral ischemia/reperfusion injury. Conclusion Tregs are involved in sevoflurane preconditioning-induced cerebral protection against ischemia/reperfusion injury.


Assuntos
Isquemia Encefálica/prevenção & controle , Precondicionamento Isquêmico , Traumatismo por Reperfusão/prevenção & controle , Sevoflurano/farmacologia , Linfócitos T Reguladores/citologia , Animais , Encéfalo/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL
17.
Adv Exp Med Biol ; 1165: 101-116, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399963

RESUMO

Kidney transplantation is a life-change measurement for the patients of end-stage renal disease (ESRD). However, the renal allograft cannot avoid initial acute kidney injury (AKI) and subsequent chronic allograft dysfunction (CAD), gradually develops fibrosis and eventually loses function. It is imperative to disclose the pathogenesis of AKI and CAD in order to facilitate interventions. We have studied the involvement of immunity, inflammation, and apoptosis in ischemia-reperfusion injury (IRI) and/or immunosuppressant induced AKI models, with associated chronic damage. Our research mainly focused on tubular epithelial cells (TECs) that are passive victims and also active participators in injury and mediate following repair or fibrosis. Targeting not only fibroblasts/myofibroblasts, but also TECs, might be a fundamental strategy to prevent and treat renal fibrosis. We have also evaluated the potential application of siRNA targeting caspase-3 and tissue protective erythropoietin derivatives, HBSP and CHBP, aiming to treat AKI and prevent CAD. Significant improvements have been obtained, but timely diagnosis and precise therapy of AKI and prevention of CAD progressing to ESRD are still very challenging. Modern technologies such as microarray and sequencing analysis have been used to identify biomarkers and potentially facilitate individual cell target treatment for transplant patients.


Assuntos
Lesão Renal Aguda , Transplante de Rim/efeitos adversos , Rim/patologia , Traumatismo por Reperfusão , Aloenxertos , Apoptose , Células Epiteliais/citologia , Fibrose , Humanos , Imunidade , Inflamação , Túbulos Renais/citologia
18.
Chem Commun (Camb) ; 55(72): 10740-10743, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31432813

RESUMO

We constructed a two-photon fluorescence ratio probe (CST) for in situ quantitative real-time detection of mitochondrial O2˙-. Fluorescence imaging showed that O2˙- was over-generated from mitochondria and conveyed to the cytoplasm via voltage-dependent anion channels in hepatic ischemia-reperfusion mice, damaging the important functional protein aconitase in the cytoplasm.


Assuntos
Fígado/metabolismo , Mitocôndrias/química , Imagem Óptica , Fótons , Traumatismo por Reperfusão/metabolismo , Superóxidos/química , Animais , Ânions/química , Ânions/metabolismo , Transporte Biológico , Corantes Fluorescentes/química , Camundongos , Mitocôndrias/metabolismo , Estrutura Molecular , Superóxidos/metabolismo
19.
Adv Exp Med Biol ; 1155: 101-112, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31468389

RESUMO

Perinatal taurine depletion and high sugar intake from weaning onward worsen cardiac damage and arterial pressure control after ischemia/reperfusion (IR) in adult male and female rats, which can be ameliorated by high taurine diets or inhibition of renin-angiotensin system. This study tests if taurine supplementation ameliorates cardiac damage and arterial pressure control in adult female rats via alterations of both cardiac and systemic renin-angiotensin system. Female Sprague-Dawley rats were fed normal rat chow and drank water alone (control, C) or water containing 3% beta-alanine (taurine depletion, TD) from conception to weaning, and female offspring were subjected to high sugar intake (normal rat chow and 5% glucose in water; CG and TDG) or the normal rat diet (CW and TDW). At 7 weeks of age, half of the rats in each group received 3% taurine in water (CW+T, CG+T, TDW+T, and TDG+T). One week later, rats were subjected to IR or Sham procedures followed by renal nerve recording, plasma and cardiac angiotensin II measurements. Cardiac angiotensin II levels significantly elevated in CG, TDW, and TDG. Further, plasma angiotensin II concentrations were significantly elevated only in the TDG, in consistent with a significant increase in renal nerve activity to juxtaglomerular cells, but not renal vessels and tubules. These abnormalities were ameliorated by short-term taurine supplementation. Thus, in adult female rats that are perinatally depleted of taurine followed by high sugar intake after weaning, taurine supplementation decreases the adverse effects of cardiac IR via inhibition of both cardiac and systemic renin-angiotensin system overactivity.


Assuntos
Isquemia Miocárdica , Sistema Renina-Angiotensina , Traumatismo por Reperfusão/fisiopatologia , Taurina/farmacologia , Animais , Açúcares da Dieta/administração & dosagem , Suplementos Nutricionais , Feminino , Gravidez , Ratos , Ratos Sprague-Dawley , Taurina/deficiência
20.
Bratisl Lek Listy ; 120(8): 558-562, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31379176

RESUMO

Genistein is a natural compound from the class of isoflavonoids found in high concentrations in legumes and soybeans. In this experimental study; we suggest that genistein might cause favorable outcomes in the hepatic surgery because of its protective effects on hepatic ischemia‒reperfusion injury (Tab. 2, Fig. 6, Ref. 28). Keywords: genistein, isoflavonoids,legumes, soybeans, hepatic surgery, ischemia‒reperfusion injury.


Assuntos
Genisteína/farmacologia , Hepatopatias/tratamento farmacológico , Fígado/cirurgia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Fígado/fisiopatologia , Ratos , Soja/química
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