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雷帕霉素对肝脏缺血再灌注中线粒体DNA损伤及修复机制的影响

, PP. 2091-2195

Keywords: ,缺血再灌注损伤,线粒体DNA,雷帕霉素,大鼠

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Abstract:

目的探讨大鼠肝缺血再灌注损伤中线粒体DNA的损伤和修复机制及雷帕霉素的干预作用。方法建立大鼠全肝缺血再灌注损伤模型,分为4组:A组:缺血30min组;B组:缺血50min组;C组:术前雷帕霉素灌胃,缺血50min组;D组:假手术组。术后24h,第3、5天分别处死各组动物,测定血清AST、ALT;取出肝脏作病理学检测;mtDNAD-loop区扩增测序,查找变异位点;RT-PCR检测肝组织内线粒体DNA聚合酶γmRNA的表达情况。结果术后早期(24h),A、B、C3组AST、ALT均升高,肝组织病理学变化较重,线粒体DNA聚合酶γmRNA表达量均升高,其中C组AST、ALT及肝组织病理学改变和线粒体DNA聚合酶γmRNA表达量明显低于B组(P<0.01);24h后3组AST、ALT均降低,A、B2组线粒体DNA聚合酶γmRNA表达量逐渐降低,C组则较A、B2组为低(P<0.01),且术后一直维持在同一水平;C组mtDNAD-loop区DNA突变率明显低于B组(P<0.01)。结论肝脏缺血再灌注损伤存在mtDNAD-loop区突变,雷帕霉素可减轻大鼠肝脏缺血再灌注的病理损害,降低mtDNA的突变率,抑制线粒体DNA聚合酶γmRNA表达量的过度升高,从而对线粒体DNA的氧化损伤起保护作用。

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