内质网及氧化应激在大鼠慢性肝损伤中的变化

The changes of endoplasmic reticulum and oxidative stress in rat chronic liver injury induced by carbon tetrachloride

目的研究内质网应激相关基因、氧化应激指标在四氯化碳诱导的大鼠慢性肝损伤中的变化。方法四氯化碳制备大鼠慢性肝损伤模型,通过测定大鼠血清ALT、AST水平,采用HE染色和TUNEL法观察肝组织病理形态和肝细胞凋亡改变,评价成模效果。检测大鼠肝脏葡萄糖调节蛋白78(GRP78)、GRP94、血红素加氧酶(HO)-1 mRNA表达及超氧化物歧化酶(SOD)、丙二醛(MDA)、还原型谷胱甘肽(GSH)变化。结果四氯化碳成功诱导了大鼠慢性肝损伤,与对照组相比,大鼠肝脏GRP78、GRP94、HO-1的表达量、MDA含量均明显增加,SOD活性、还原型GSH显著降低。结论四氯化碳诱导大鼠慢性肝损伤时,内质网应激相关基因的表达增加,氧化应激指标亦发生改变,表明内质网应激、氧化应激共同参与了大鼠慢性肝损伤过程。

Objective To investigate the expression of endoplasmic reticulum stress （ERS） related genes and the changes of oxidative stress （OS） in the development of chronic liver injury induced by carbon tetraehloride （CCl4） in rats. Methods Male SD rats were randomly allocated to establish the model of chronic liver injury by administration of CCl4 intraperitoneally. The aspartate aminotransferase （ALT） and alanine aminotransferase （AST） in serum were analyzed. Additionally, histopathological changes and hepatocyte apoptosis were detected by HE and TUNEL methods. The expressions of GRP78, GRP94 and HO-1 were determined by RT-PCR. The activities of SOD, MDA and reduced-GSH were analyzed by biochemical methods. Results The rat model of chronic liver injury induced by CCl4 was successfully established. The level of ALT and AST in serum increased significantly compared with the control group, and a marked hepatic damage was confirmed. Simultaneously the expression of GRP78, GRP94 and HO-1 mRNA increased specifically. The elevation of MDA activity was detected, however, SOD and GSH reduced remarkably. Conclusion The elevated expression of relevant genes of ERS and the action of OS occurred after CCl4 treatment, which indicates both ERS and OS participate in the process of the chronic liver injury caused by CCl4 in rats.