AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expres...AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expression and cell apoptosiswere detected in rat model of hepatic/ renalischemia-reperfusion injury.ELISA,immunohist-ochemistry and TUNEL were used.Someischemia-reperfusion rats were treated with anti-P-selectin mAb.RESULTS Hepatic/renal function insuffic-iency,up-regulated expression of P-selectin inplasma and hepatic/renal tissue,hepatic/renalhistopathological damages and cell apoptosiswere found in rats with hepatic/renal ischemia-reperfusion injury,while these changes becameless conspicuous in animals treated with anti-P-selectin mAb.CONCLUSION P-selectin might mediateneutrophil infiltration and cell apoptosis andcontribute to hepatic/renal ischemia-reperfusioninjury,anti-P-selectin mAb might be an efficientapproach for the prevention and treatment ofhepatic/renal ischemia-reperfusion injury.展开更多
The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury（IRI） in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for ...The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury（IRI） in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups： sham-operated group（sham）, IRI＋saline group（IRI group）, IRI＋Fenofibrate（FEN） group. Normal saline or Fenofibrate（3 mg/kg） was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8（IL-8）, tumor necrosis factor alpha（TNF-α） and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B（PI3K/Akt） signaling and peroxisome proliferator-activated receptor-α（PPAR-α） were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI.展开更多
Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were random...Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-展开更多
BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. ...BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE： To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi＇an Jiaotong University from June 2007 to September 2008. MATERIALS： SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK （Thr183/Tyr185） polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 （XRCC1） and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS： A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group （I/R group） were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group （pre-SP group） was given 10 μL SP600125 （3 μg/μL）. Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS： Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased （P 〈 0.01）. Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased （P 〈 0.01）. Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased （P 〈 0.05） following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group （P 〈 0.05）. Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region （r = -0.983, -0.953, P 〈 0.01）. CONCLUSION： SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.展开更多
Objective： To investigate the impact of a traditional Chinese medicinal compound known as Fufang Shenhua Tablet （复方肾华片, SHP） on the expression of Toll-like receptors （TLRs） during renal ischemia-reperfusion ...Objective： To investigate the impact of a traditional Chinese medicinal compound known as Fufang Shenhua Tablet （复方肾华片, SHP） on the expression of Toll-like receptors （TLRs） during renal ischemia-reperfusion injury （IRI）-induced acute kidney injury （AKI） in rats. Methods： A total of 28 Wistar rats were randomly divided into five groups： （1） pseudo-operation control group, （2） ischemia-reperfusion model group, （3） Astragaloside group, （4） high-dose SHP group, and （5） low-dose SHP group. There were four rats in the pseudo-operation group and six rats in each of the other groups. The accepted ischemia-reperfusion model was established after a 7-day gavage intervention, and pathological changes and renal function were observed, using an enzyme-linked immunosorbent assay （ELISA） to detect interleukin 8 （IL-8） and interferon gamma （IFN-r） levels, as well as immunohistochemical staining to detect altered levels of TLR2 and TLR4 expression in renal tissue. Results： After 24 h, renal pathological damage and the expression levels of serum creatinine （Scr）, IL-8, IFN- r, TLR2, and TLR4 were significantly higher in the model group as compared with the pseudo-operation group （P〈0.05）. In addition, at 24 h the above indicators decreased significantly in the Astragaloside group, high- dose SHP group and low-dose SHP group as compared with the ischemia-reperfusion model group （P〈0.05）. TLR2 and TLR4 expression levels were significantly reduced in the SHP treatment and Astragaloside group as compared with the pseudo-operation group （P〈0.05）. Further, the high-dose SHP group showed significantly less renal damage score and decreased levels of TLR expression than those of low-dose SHP group and Astragaloside group （all P〈0.05）. Conclusion： SHP can alleviate the renal structural and functional damage caused by IRI-induced AKI in rats by reducing the damage of renal pathology, which may reduce inflammatory cytokine levels by downregulating the expression of TLRs in renal tissue in a dose-dependent manner.展开更多
目的建立幼鼠肾脏缺血再灌注损伤(RIRI)模型,探讨亚低温环境诱导的冷休克蛋白RBM3对RIRI的作用。方法将7 d SD幼鼠24只随机分为正常对照组(NC组)、假手术组(Sham组)、RIRI未亚低温组(NH组)、RIRI亚低温组(TH组),每组6只。建立肾脏RIRI模...目的建立幼鼠肾脏缺血再灌注损伤(RIRI)模型,探讨亚低温环境诱导的冷休克蛋白RBM3对RIRI的作用。方法将7 d SD幼鼠24只随机分为正常对照组(NC组)、假手术组(Sham组)、RIRI未亚低温组(NH组)、RIRI亚低温组(TH组),每组6只。建立肾脏RIRI模型,进行全身亚低温治疗;检测血肌酐(SCr)、半胱氨酸蛋白酶抑制剂C(CysC)水平;取左肾组织行HE染色,观察病理学变化,取右肾组织用qPCR检测YAP1和NRF2基因表达情况;用Western Blot检测RBM3蛋白表达量。结果NC组与Sham组的SCr、CysC水平比较,差异无统计学意义(P>0.05);NH组与TH组的SCr、CysC水平显著高于NC组,NH组的SCr、CysC水平显著高于TH组(P<0.05)。NH组和TH组的病理组织评分高于NC组,NH组的病理组织评分高于TH组(P<0.05)。TH组的YAP1、NRF2基因表达显著高于NC组和NH组(P<0.05)。TH组的RBM3蛋白表达量明显高于NC组和NH组(P<0.05)。结论全身亚低温诱导的RBM3对幼鼠RIRI有一定的保护作用,这种保护作用可能与低温诱导的RBM3降低了炎症反应有关。展开更多
基金the Scientific Foundation of Ministry of Health of China,No.98-2-283Shanghai Natural Science Foundation,No.98ZB14025
文摘AIM To evaluale the potential role of P-selectinand anti-P-selectin monoclonal antibody(mAb)in apoptosis during hepatic/renal ischemia-reperfusion injury.METHODS Plasma P-selectin level,hepatic/renal P-selectin expression and cell apoptosiswere detected in rat model of hepatic/ renalischemia-reperfusion injury.ELISA,immunohist-ochemistry and TUNEL were used.Someischemia-reperfusion rats were treated with anti-P-selectin mAb.RESULTS Hepatic/renal function insuffic-iency,up-regulated expression of P-selectin inplasma and hepatic/renal tissue,hepatic/renalhistopathological damages and cell apoptosiswere found in rats with hepatic/renal ischemia-reperfusion injury,while these changes becameless conspicuous in animals treated with anti-P-selectin mAb.CONCLUSION P-selectin might mediateneutrophil infiltration and cell apoptosis andcontribute to hepatic/renal ischemia-reperfusioninjury,anti-P-selectin mAb might be an efficientapproach for the prevention and treatment ofhepatic/renal ischemia-reperfusion injury.
基金supported by the National Natural Science Foundation of China(No.81070557)
文摘The aim of this study was to investigate the possible beneficial effects of Fenofibrate on renal ischemia-reperfusion injury（IRI） in mice and its potential mechanism. IRI was induced by bilateral renal ischemia for 60 min followed by reperfusion for 24 h. Eighteen male C57BL/6 mice were randomly divided into three groups： sham-operated group（sham）, IRI＋saline group（IRI group）, IRI＋Fenofibrate（FEN） group. Normal saline or Fenofibrate（3 mg/kg） was intravenously injected 60 min before renal ischemia in IRI group and FEN group, respectively. Blood samples and renal tissues were collected at the end of reperfusion. The renal function, histopathologic changes, and the expression levels of pro-inflammatory cytokines [interleukin-8（IL-8）, tumor necrosis factor alpha（TNF-α） and IL-6] in serum and renal tissue homogenate were assessed. Moreover, the effects of Fenofibrate on activating phosphoinositide 3 kinase/protein kinase B（PI3K/Akt） signaling and peroxisome proliferator-activated receptor-α（PPAR-α） were also measured in renal IRI. The results showed that plasma levels of blood urea nitrogen and creatinine, histopathologic scores and the expression levels of TNF-α, IL-8 and IL-6 were significantly lower in FEN group than in IRI group. Moreover, Fenofibrate pretreatment could further induce PI3K/Akt signal pathway and PPAR-α activation following renal IRI. These findings indicated PPAR-α activation by Fenofibrate exerts protective effects on renal IRI in mice by suppressing inflammation via PI3K/Akt activation. Thus, Fenofibrate could be a novel therapeutic alternative in renal IRI.
文摘Objective To investigate the effect and mechanism of adrenomedullin ( AM ) on apoptosis of renal tubular epithelial cell in rats induced by renal ischemia reperfusion injury. Methods Thirty-two Wistar rats were randomly divided into 4 groups: control group,IRI group, empty plasmid group and AM group. One week after re-
基金Supported by: the National Natural Science Foundation of China, No. 30571790
文摘BACKGROUND： Recent studies have shown that the selective inhibitor of c-Jun N-terminal kinases （JNKs） signaling pathway, SP600125, exhibits neuronal protective effects in a rat model of brain ischemia/reperfusion. OBJECTIVE： To determine the mechanisms of neuroprotective effects of SP600125 in a rat model of brain ischemia/reperfusion, and determine the role of the JNK signaling pathway in SP600125-induced effects. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Animal Experiment Center, Medical School of Xi＇an Jiaotong University from June 2007 to September 2008. MATERIALS： SP600125 was provided by Biosource, USA; rabbit anti-phospho-JNK （Thr183/Tyr185） polyclonal antibody from Cell Signaling Technology, USA; rabbit anti-X-ray repair cross-complementing protein 1 （XRCC1） and anti-Ku70 polyclonal antibodies from Santa Cruz Biotechnology, USA; and TUNEL kit from Beijing Huamei Biology, China. METHODS： A total of 108 male, 4-month-old, Sprague Dawley rats were randomly assigned to three groups, with 36 rats per group. The sham operation group and ischemia/reperfusion group （I/R group） were intracerebroventricularly injected with 10 μL 1% DMSO. The SP600125-treated group （pre-SP group） was given 10 μL SP600125 （3 μg/μL）. Thirty minutes later, brain ischemia was induced in the I/R and pre-SP groups using the four-vessel occlusion method. Specifically, whole brain ischemia was induced for 6 minutes, and the clips were released to restore carotid artery blood flow. Rats from each group were observed at 2, 6, 12, 24, 48, and 72 hours, with 6 rats for each time point. The sham operation group was treated with the same surgical exposure procedures, with exception of occlusion of the carotid artery. MAIN OUTCOME MEASURES： Hematoxylin-eosin staining was used to observe neuronal survival in the hippocampal CA1 region, TUNEL was used to detect apoptosis in the hippocampal CA1 region, and immunohistochemistry was used to detect expression of phospho-JNK, XRCC1, and Ku70. RESULTS： Following brain ischemia/reperfusion, neuronal survival significantly decreased, and the number of apoptotic cells significantly increased （P 〈 0.01）. Compared with the I/R group, neuronal survival significantly increased in the pre-SP group, and the number of apoptotic cells significantly decreased （P 〈 0.01）. Expression of phospho-JNK increased, and XRCC1 and Ku70 significantly decreased （P 〈 0.05） following ischemia/reperfusion. Compared with the I/R group, expression of phospho-JNK decreased, and XRCC1 and Ku70 significantly increased in the pre-SP group （P 〈 0.05）. Correlation analysis revealed an inverse correlation between phospho-JNK gray value and XRCC1 and Ku70 gray values in the hippocampal CA1 region （r = -0.983, -0.953, P 〈 0.01）. CONCLUSION： SP600125 treatment decreased apoptosis induced by global brain ischemia/reperfusion in the rat hippocampal CA1 region. Results suggested that the neuroprotective effects were due to inhibited phosphorylation of JNK and reduced down-regulation of XRCC1 and Ku70.
基金Supported by the National Natural Science Foundation of China(No.81072914 and 81273968)Major Project Foundation of National Science and Technology(No.2010ZX9102-204)Traditional Chinese Medicine Research Grant for Military Organization(No.10ZYZ255)
文摘Objective： To investigate the impact of a traditional Chinese medicinal compound known as Fufang Shenhua Tablet （复方肾华片, SHP） on the expression of Toll-like receptors （TLRs） during renal ischemia-reperfusion injury （IRI）-induced acute kidney injury （AKI） in rats. Methods： A total of 28 Wistar rats were randomly divided into five groups： （1） pseudo-operation control group, （2） ischemia-reperfusion model group, （3） Astragaloside group, （4） high-dose SHP group, and （5） low-dose SHP group. There were four rats in the pseudo-operation group and six rats in each of the other groups. The accepted ischemia-reperfusion model was established after a 7-day gavage intervention, and pathological changes and renal function were observed, using an enzyme-linked immunosorbent assay （ELISA） to detect interleukin 8 （IL-8） and interferon gamma （IFN-r） levels, as well as immunohistochemical staining to detect altered levels of TLR2 and TLR4 expression in renal tissue. Results： After 24 h, renal pathological damage and the expression levels of serum creatinine （Scr）, IL-8, IFN- r, TLR2, and TLR4 were significantly higher in the model group as compared with the pseudo-operation group （P〈0.05）. In addition, at 24 h the above indicators decreased significantly in the Astragaloside group, high- dose SHP group and low-dose SHP group as compared with the ischemia-reperfusion model group （P〈0.05）. TLR2 and TLR4 expression levels were significantly reduced in the SHP treatment and Astragaloside group as compared with the pseudo-operation group （P〈0.05）. Further, the high-dose SHP group showed significantly less renal damage score and decreased levels of TLR expression than those of low-dose SHP group and Astragaloside group （all P〈0.05）. Conclusion： SHP can alleviate the renal structural and functional damage caused by IRI-induced AKI in rats by reducing the damage of renal pathology, which may reduce inflammatory cytokine levels by downregulating the expression of TLRs in renal tissue in a dose-dependent manner.
文摘目的建立幼鼠肾脏缺血再灌注损伤(RIRI)模型,探讨亚低温环境诱导的冷休克蛋白RBM3对RIRI的作用。方法将7 d SD幼鼠24只随机分为正常对照组(NC组)、假手术组(Sham组)、RIRI未亚低温组(NH组)、RIRI亚低温组(TH组),每组6只。建立肾脏RIRI模型,进行全身亚低温治疗;检测血肌酐(SCr)、半胱氨酸蛋白酶抑制剂C(CysC)水平;取左肾组织行HE染色,观察病理学变化,取右肾组织用qPCR检测YAP1和NRF2基因表达情况;用Western Blot检测RBM3蛋白表达量。结果NC组与Sham组的SCr、CysC水平比较,差异无统计学意义(P>0.05);NH组与TH组的SCr、CysC水平显著高于NC组,NH组的SCr、CysC水平显著高于TH组(P<0.05)。NH组和TH组的病理组织评分高于NC组,NH组的病理组织评分高于TH组(P<0.05)。TH组的YAP1、NRF2基因表达显著高于NC组和NH组(P<0.05)。TH组的RBM3蛋白表达量明显高于NC组和NH组(P<0.05)。结论全身亚低温诱导的RBM3对幼鼠RIRI有一定的保护作用,这种保护作用可能与低温诱导的RBM3降低了炎症反应有关。
