内质网应激在小鼠急性肝损伤中的作用机制

发布时间：2018-11-26 19:19

【摘要】：目的探讨内质网应激在四氯化碳(CCl4)诱导的小鼠急性肝损伤中的变化及作用机制。方法C57BL/6小鼠30只,随机分为模型组和对照组各15只,模型组给予20%CCl4(0.1 m L/10 g)腹腔注射制备小鼠急性肝损伤模型,对照组给予橄榄油溶液腹腔注射(0.1 m L/10 g)作为正常对照。采用病理染色观察小鼠肝组织病理形态学和肝细胞内质网应激相关蛋白以及凋亡蛋白的表达情况,采用蛋白质印迹法测定小鼠肝脏内质网应激相关蛋白以及凋亡相关蛋白的表达变化趋势。结果 CCl4腹腔注射后8 h,模型组小鼠肝脏出现明显的损伤,肝组织GRP78蛋白以及cleaved caspase-12表达量显著升高(P0.05),cleaved caspase-3表达量亦显著升高(P0.05);TUNEL法检测结果均显示模型组肝脏有严重损伤,大量肝细胞发生凋亡,凋亡指数较对照组明显升高(P0.05),而PCNA染色显示模型组肝细胞增殖指数明显少于对照组(P0.05);相蛋白质印迹显示,模型组内质网应激相关蛋白以及凋亡蛋白表达量均明显升高,同时伴有线粒体细胞色素c的释放,而促细胞增殖蛋白p-Akt、PCNA表达量明显降低。结论内质网应激反应介导的线粒体细胞凋亡通路参与了CCl4诱导的小鼠急性肝损伤的发病过程。
[Abstract]:Objective To investigate the changes and mechanism of endoplasmic reticulum stress in acute liver injury induced by carbon tetrachloride (CCl4). Methods Thirty C57BL/ 6 mice were randomly divided into two groups: model group and control group. The model group was given 20% CCl4 (0.1 m L/ 10 g) to prepare acute liver injury model of mice. The control group was given an intraperitoneal injection of olive oil solution (0.1 m L/ 10 g) as the normal control. The expression of endoplasmic reticulum stress-related protein and apoptosis protein in the liver of mice was observed by pathological staining, and the expression trend of the related protein and apoptosis-related protein in the liver of mice was determined by Western blot. Results The expression of the liver tissue GRP78 protein and the clear caspase-12 increased significantly (P0.05). The results of the TUNEL method showed that the liver of the model group was severely damaged. In the model group, the expression of the endoplasmic reticulum stress-related protein and the apoptosis protein of the model group was significantly higher than that in the control group (P0.05). At the same time, the release of cytochrome c was accompanied by the release of cytochrome c, and the expression of p-Akt and PCNA in the pro-cell proliferation was significantly lower. Conclusion Endoplasmic reticulum stress-mediated apoptosis pathway is involved in the pathogenesis of acute liver injury induced by CCl4.
【作者单位】：广东省罗定市人民医院消化内科;中山大学附属第三医院消化内科;
【分类号】：R575

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