失血性休克大鼠肠上皮细胞PGC-1基因表达改变及意义

摘要

Objective To study changes of expressions of peroxisome proliferator - activated receptor γ coactivator-1 gene( PGC-1 gene) of small intestinal epithelia in rats with hemorrhagic shock,so as to study effects of the transcriptional coactivator PGC-I on expressions of nuclear and mitochondrial genome coding the respiratory chain subunits. Methods The expressions of intestinal PGC-1 gene were measured by means of RT-PCR. The changes of expressions of PGC-1 protein were examined by Western-blot. Results The RT-PCR results showed that the expression of PGC-1 mRNA increased gradually at 1 hour,2 hour,3 hour after shock, decreased gradually and lowered significantly at 5 hour in hemorrhagic shock group compared with control group ( P＜ 0. 05 ) . The expression of PGC-1 protein increased at 2 hour, then decreased at 3 hour after hemorrhagic shock and lowered markedly at 5 hour in hemorrhagic shock group compared with control group. Conclusion The expressions of PGC-1 mRNA and protein of intestinal epithelial cells in hemorrhagic shock rats increase in the early stage and decrease in the late stage. These results show that PGC-1 is highly sensitive to ischemia and hypoxia. PGC-1 protein is up-regulated in early ischemia and hypoxia stage , which may be related to its expression increase. PGC-1 protein decrease at 5 hour after hemorrhagic shock,which may result from dysfunction of mitochondrial energy metabolism and synthesis reduction of PGC-1 protein of intestinal epithelial cells .%目的 探讨失血性休克大鼠肠上皮细胞核转录因子过氧化物酶体增殖物激活受体γ辅激活因子-1(PGC-1)基因表达的改变,以探讨核转录因子对编码呼吸链亚基的细胞核基因组和线粒体基因组表达的影响.方法 采用转录-聚合酶链式反应(RT-PCR)方法观察失血性休克大鼠肠上皮细胞PGC-1基因mRNA量的改变,用Western-blot法检测肠上皮细胞PGC-1蛋白的表达变化.结果 正常大鼠肠上皮细胞PGC-1 mRNA有较低程度表达,失血性休克1小时大鼠肠上皮细胞PGC-1 mRNA表达开始增加,2小时达高峰并维持到3小时,后又开始减弱,到休克晚期5小时PGC-1mRNA表达显著弱于休克前(P<0.05).正常大鼠肠上皮细胞PGC-1蛋白含量较低.失血性休克1小时大鼠肠上皮细胞PGC-1蛋白含量基本没有变化.失血性休克2小时,即休克中期PGC-1蛋白表达增强,后又渐减弱,失血性休克5小时已明显弱于休克前.结论 失血性休克早期大鼠肠上皮细胞核转录因子PGC-1基因表达增强,晚期减弱,PGC-1基因表达对缺血缺氧敏感,缺血缺氧早期肠上皮细胞PGC-1蛋白表达上调,可能与PGC-1 mRNA的上调有关.休克晚期PGC-1蛋白表达减少可能与线粒体能量代谢障碍时细胞蛋白合成减少有关.