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目的:观察caspase-12抑制剂Z-ATAD-FMK对百草枯染毒大鼠肝脏caspase-12蛋白表达和肝细胞凋亡的影响,以及通过血清SOD和MDA的检测,探讨其对百草枯中毒大鼠肝脏保护作用和对机体氧化应激反应的作用。方法:50只健康Wistar大鼠随机分三组:A组为正常对照组;B组为模型组(PQ染毒);C组抑制剂组(PQ/Z-ATAD-FMK),于3d、7d处死B组和C组各10只大鼠。取血检测ALT、TBIL、SOD和MDA;HE染色观察肝组织病理学变化;免疫组化法检测caspase-12蛋白;二苯胺法检测细胞凋亡率。SPSS18.0统计分析。结果:Z-ATAD-FMK抑制剂组ALT、TBIL、MDA值低于模型组(P<0.05),SOD高于模型组(P<0.05);caspase-12蛋白表达和细胞凋亡率亦低于模型组(P<0.05);HE染色显示凋亡和坏死程度也较模型组轻。结论:Caspase-12抑制剂Z-ATAD-FMK能减少百草枯中毒大鼠肝脏caspase-12蛋白表达和肝细胞凋亡率,减轻肝细胞坏死,对肝脏具有保护作用,同时可以抑制百草枯中毒大鼠的氧化应激反应。
OBJECTIVE: To observe the effects of caspase-12 inhibitor Z-ATAD-FMK on the expression of hepatic caspase-12 protein and hepatocyte apoptosis in paraquat-induced rats and the detection of SOD and MDA by paraquat-12 Protective effects of rat liver and its effect on oxidative stress in the body. Methods: Fifty healthy Wistar rats were randomly divided into three groups: group A was normal control group; group B was model group (PQ); group C inhibitor (PQ / Z-ATAD-FMK) Ten rats in groups B and C were sacrificed. Blood samples were taken for ALT, TBIL, SOD and MDA. Liver histopathological changes were observed by HE staining. Caspase-12 protein was detected by immunohistochemistry and apoptotic rate by diphenylamine method. SPSS18.0 statistical analysis. Results: The levels of ALT, TBIL and MDA in Z-ATAD-FMK inhibitor group were lower than those in model group (P <0.05) and SOD were higher than those in model group (P <0.05), while the expression of caspase- Model group (P <0.05). The HE staining showed that the apoptosis and necrosis were also lighter than the model group. Conclusion: Z-ATAD-FMK, a Caspase-12 inhibitor, can reduce the hepatic caspase-12 protein expression and hepatocyte apoptosis rate in paraquat-poisoned rats, reduce the necrosis of hepatocytes and protect the liver. At the same time, it can inhibit paraquat poisoning Oxidative stress in rats.