P38MAPK抑制剂对急性肝衰竭大鼠内质网应激反应性凋亡的作用

Effect of P38MAPK inhibitor on endoplasmic reticulum stressinduced hepatocyte apoptosis in rats with acute liver failure

目的:观察P38MAPK抑制剂SB203580对急性肝衰竭大鼠肝组织Caspase12蛋白表达及肝细胞凋亡的影响,探讨其对急性肝衰竭大鼠肝脏保护作用的机制.方法:72只健康Wistar大鼠随机分3组:对照组(注射生理盐水)、模型组(注射D-Gal/LPS)、抑制剂组(D-Gal/LPS+SB203580).按时间点分为3个亚组,每亚组8只.取血检测丙氨酸氨基转移酶(alanine aminotransferase,ALT)、总胆红素(total bilirubin,TBIL);HE染色观察肝组织病理学变化;免疫组织化学法检测Caspase12蛋白;二苯胺法检测细胞凋亡率.SPSS18.0统计分析.结果:抑制组12 h肝功、Caspase12蛋白表达和细胞凋亡率均低于模型组;18 h Caspase12蛋白表达与模型组差异无统计学意义,细胞凋亡率高于模型组;模型组12 h出现坏死,抑制组18 h出现坏死.结论:P38MAPK抑制剂SB203580能减少肝衰竭大鼠Caspase12蛋白表达和肝细胞凋亡率,减轻肝细胞坏死,对急性肝衰竭大鼠的肝脏具有保护作用.

AIM： To observe the effect of P38 MAPK inhibitor SB203580 on Caspase12 protein expression and apoptosis of hepatocytes in rats with acute hepat-ic failure, and to explore the mechanism underly-ing its protective effect on acute hepatic failure. METHODS： Seventy-two healthy Wistar rats were randomly divided into three groups： a con-trol group（injected with normal saline）, a model group（injected with D-galactosamine/lipopoly-saccharide, D-Gal/LPS）, and an inhibitor group（injected with D-Gal/LPS ＋ SB203580）. Each group was further divided into three subgroups for testing at different time points, with 8 rats in each subgroup. Blood samples were collected for the determination of alanine aminotransfer-ase（ALT） and total bilirubin（TBIL）. HE staining was performed to observe the liver pathologi-cal changes. Immunohistochemical assay was performed to detect the expression of Caspase12 protein. The diphenylamine method was used to detect the apoptosis rate. RESULTS： The liver function, Caspase12 pro-tein expression and apoptosis rate in the inhibi-tor group at 12 h were lower than those in the model group. Caspase12 protein expression at 18 h in the inhibitor group had no significant difference with that in the model group, while the apoptosis rate was significantly higher in the inhibitor group than in the model group. Necro-sis occurred in the model group at 12 h, and in the inhibitor group at 18 h. CONCLUSION： P38 MAPK inhibitor SB203580 can reduce the expression of Caspase12 protein, inhibit the endoplasmic reticulum stress-medi-ated hepatocyte apoptosis, reduce the necrosis of liver cells and play a protective effect against acute hepatic failure.