| 克霉唑抗大鼠肝缺血再灌注损伤机制研究 |
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| 引用本文： | 陈杰,许静,袁芳,夏延哲,曹媛,陈孝.克霉唑抗大鼠肝缺血再灌注损伤机制研究[J].现代食品与药品杂志,2011(11). |
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| 作者姓名： | 陈杰 许静 袁芳 夏延哲 曹媛 陈孝 |
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| 作者单位： | 中山大学附属第一医院药学部;南方医科大学附属第三医院药剂科;广东药学院药科学院药理系; |
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| 基金项目： | 国家自然科学基金(编号:30972917); 广东省自然科学基金(编号:8451008901000788); 广东省医学科研基金(编号:A2009163) |
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| 摘 要： | 目的研究孕烷X受体(pregnane X receptor,PXR)介导克霉唑抗大鼠肝缺血再灌注损伤作用及其机制。方法 SD大鼠随机分成4组,分别为假手术组、缺血再灌注组、克霉唑低剂量组和克霉唑高剂量组。以谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)、超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MDA)含量及热休克蛋白70(HSP70)蛋白表达等为观察指标,用终浓度分别为25 mg/kg和50 mg/kg的克霉唑预处理大鼠5 d,5 h后观察其对肝缺血再灌注损伤的作用。结果 PXR特异性强诱导剂克霉唑,与假手术组比,能明显诱导CYP3A1基因表达,表现为ALT、AST和LDH显著降低(P<0.05),且呈剂量依赖性,SOD和GSH-Px活性分别升高,MDA显著降低,对抗氧自由基ROS损伤,上调HSP70表达(P<0.05),表现出强大的抗缺血再灌注损伤作用。结论克霉唑预具有较好抗肝缺血再灌注损伤的保护作用,其机制可能在PXR介导下,拮抗ROS损伤及内源性保护蛋白HSP70表达上调有关。
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| 关 键 词： | 克霉唑 孕烷X受体 缺血再灌注损伤 |
Clotrimazole Protects Liver against Normothermic Ischemia-reperfusion Injury in Rats |
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| CHEN Jie,XU Jing,YUAN Fang,XIA Yan-zhe,CAO Yuan,CHEN Xiao.Clotrimazole Protects Liver against Normothermic Ischemia-reperfusion Injury in Rats[J].JOurnal of Modern Food and Pharmaceuticals,2011(11). |
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| Authors: | CHEN Jie XU Jing YUAN Fang XIA Yan-zhe CAO Yuan CHEN Xiao |
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| Institution: | CHEN Jie1,XU Jing2,YUAN Fang3,XIA Yan-zhe1,CAO Yuan1,CHEN Xiao1(1.Department of Pharmacy,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong 510080,China,2.Department of Pharmacy,the Third Affiliated Hospital of Southern Medical University,Guangdong 510630,3.College of Pharmacy,Guangdong Pharmaceutical University,510006,China) |
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| Abstract: | Objective To investigate the possible role of the pregnane X receptor(PXR) in hepatic ischemia-reperfusion injury in rats using clotrimazole(CTZ),a strong PXR transactivator.Methods Male Sprague-Dawley rats were divided into 4 groups of 8 each: sham-treated,control,and CTZ-treated animals.The rats were pretreated with 25 mg/kg and 50 mg/kg CTZ for 5 d,respectively.Control and CTZ treated animals were subjected to 30 min of normothermic ischemia of the whole liver followed by 5 h of reperfusion,and the anima... |
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| Keywords: | clotrimazole pregnane X receptor ischemia-reperfusion injury |
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