内质网应激分子伴侣GRP78在大鼠缺血再灌注损伤肝脏中的表达

目的:观察内质网应激相关分子葡萄糖调节蛋白78(GRP78)在大鼠缺血再灌注损伤肝脏组织中的表达水平.方法:将24只健康雄性SD大鼠随机均分为假手术组,单纯肝缺血组(肝缺血30 min+再灌注0h),再灌注6h组(肝缺血30 min+再灌注6h)和再灌注12h组(肝缺血30 min+再灌注12h).分别检测各组血清丙氨酸转氨酶(ALT)和门冬氨酸转氨酶(AST)水平；肝组织病理学、凋亡情况及GRP78 mRNA表达水平.结果:与对照组比较,各实验组大鼠肝缺血后出现明显的肝组织损伤,且随着再灌注时间的延长损伤加重,表现为血清ALT和AST水平升高,明显的肝组织病理学改变,肝细胞凋亡率增加,各组间计量指标的差异均有统计学意义(均P＜0.05).大鼠肝组织GRP78 mRNA变化趋势与上述指标一致,缺血后表达明显上调,且随着再灌注时间延长而逐渐升高,各组间差异均有统计学意义(均P＜0.05).结论:缺血再灌注损伤肝脏组织中GRP78表达上调,但其具体作用还有待于探明.

Expression of GRP78, a molecular chaperone of endoplasmic reticulum stress response, in rat liver with ischemia-reperfusion injury

Objective: To observe the expression of the glucose-regulated protein 78 (GRP78), an endoplasmic reticulum stress (ERS) related molecule, in the rat liver tissues injured by ischemia-reperfusion. Methods: Twenty-four healthy male SD rats were equally randomized into sham operation group, hepatic ischemia alone group (30 min hepatic ischemic followed by no reperfusion), 6-h reperfusion group (30 min hepatic ischemic followed by 6-h reperfusion) and 12-h reperfusion group (30 min hepatic ischemic followed by 12-h reperfusion). The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of each group of rats were measured, and the pathological changes, apoptosis and GRP78 mRNA expression in rats’ liver tissues were also determined. Results: Compared with control group, all the experimental groups presented obvious hepatic tissue injuries after ischemia, and the injuries were exacerbated with the prolongation of reperfusion period, as evidenced by the increased serum levels of ALT and AST, remarkable pathological changes in the hepatic tissues, and elevated apoptotic rates, with all the differences for the quantitative parameters among groups reaching statistical significance (all P<0.05). The GRP78 mRNA expression in rats’ liver tissues, similar to the patterns of the above parameters, was significantly increased after hepatic ischemia and aggravated as reperfusion time went on, with the differences reaching statistical significance among groups (all P<0.05). Conclusion: The GRP78 expression is up-regulated in the liver tissue injured by ischemia-reperfusion, however, its exact role in this process remains to be verified.