Caspase-12抑制剂对百草枯中毒大鼠肝损伤的保护作用

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(P0.05),SOD高于模型组(P0.05);caspase-12蛋白表达和细胞凋亡率亦低于模型组(P0.05);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。

Protective Effect of Caspase-12 Inhibitor on Liver Injury in Paraquat Poisoning Rats

Objective:To observe the influence of Caspase-12 inhibitor Z-Ala-Thr-Ala-Asp-fluoromethyl ketone (Z-ATADFMK) on the caspase-12 protein expression and apoptosis of liver cells of rats exposed to paraquat, and to explore its protective effects on paraquat poisoning liver of rats and its role in oxidative stress.Methods:50 healthy Wistar rats were randomly divided into 3 groups: A group (injected with normal saline), B group (injected with paraquat) and C group (injected with paraquat and Z-ATAD-FMK). 10 rats of group B and C were sacrificed respectively on the 3rd day and 7th day. The blood samples were obtained to check alanine aminotransferase (ALT), total bilirubin (TBIL), SOD and MDA in serum. HE staining was performed to observe the liver pathological changes. The immunohistochemical assay was performed to detect the expression of caspase-12 protein. The diphenylamine method was used to detect the apoptosis rate. SPSS18.0 was used for the statistical analysis.Results:ALT, TBIL and MDA in C group were lower than those of B group, while SOD in C group was higher than that of B group. The caspase-12 protein expression and apoptosis rate in C group were lower than those of B group. HE staining showed that the apoptosis and necrosis in hepatocytes in C group were also lighter than those of B group.Conclusion:Caspase-12 inhibitor Z-ATAD-FMK can reduce the expression of caspase-12 protein and apoptosis rate in liver of paraquat poisoning rats, and also reduce hepatocellular necrosis. We concluded that Z-ATAD-FMK might have a protective effect on the liver and meanwhile, the oxidative stress in paraquat poisoning rats could be inhibited by it.