艾塞那肽对糖耐量减低大鼠肝脏内质网应激标志性蛋白C/EBP同源蛋白表达的作用

Effects of exendin-4 on expression of endoplasmic reticulum stress marker C/EBP homologous protein in hepatocyte of rats with impaired glucose tolerance

目的 探讨胰高血糖素样肽-1(GLP-1)受体激动剂艾塞那肽对糖耐量减低(IGT)大鼠肝细胞内质网应激标志性蛋白C/EBP同源蛋白(CHOP)表达的作用。方法 42只雄性Wistar大鼠,随机分为正常耐量组(NGT组,14只),IGT组(28只),NGT组予常规饲料,IGT组予高糖高脂饲料。12周时口服葡萄糖耐量试验(OGTT)2h血糖(2hPG)介于7.8～11.1mmol/L大鼠为IGT造模成功,成模后从IGT组随机抽取1/2数量设为艾塞那肽干预组(Ex组),每日2次皮下注射艾塞那肽(10μg/kg);另外1/2数量设为IGT对照组。NGT组及IGT对照组均给予等体积0.9%氯化钠注射液皮下注射。8周后反转录聚合酶链反应(RT-PCR)技术检测3组肝脏CHOPmRNA的表达;各组间两两比较采用单因素方差分析(ANOVA),LSD-t检验。结果 与NGT组比较,IGT对照组及Ex组大鼠肝脏CHOPmRNA表达升高,差异有统计学意义(均P<0.05)。艾塞那肽干预8周后,与同期IGT对照组比较,Ex组CHOPmRNA表达降低,差异有统计学意义(P<0.05);与干预前Ex组比较降低,差异有统计学意义(P<0.05)。结论 艾塞那肽可以降低肝细胞内质网应激,具有改善肝细胞损伤的危险因素的作用。

Objective To investigate the effects of glucagon-like peptide-1 agonist （exendin-4） on hepatocyte expression of C/EBP homologous protein （CHOP）, an endoplasmic reticulum stress marker, in rats with impaired glucose tolerance （IGT）. Methods Forty-two male Wistar rats were randomly assigned into normal glucose tolerance group （NGT group, n=14） to be fed on routine diet and IGT group （n=28） to be fed on high-sugar high-fat diet. At week 12, IGT models were considered successful based on the level of 2-hour peripheral blood glucose （2 hPG） in oral glucose tolerance test between 7.8 and 11.1 mmol/L. Following establishment of models, half of the rats were allocated to intervention group （Ex group） and were subject to exendin-4 subcutaneous injection （10 μg/kg, twice daily）, with the remaining half set as IGT control group. Both NGT group and IGT control group were given same volume of normal saline for injection as in the Ex group. At week 8, RT-PCR was employed to analyze the hepatocyte expression of CHOP mRNA. Inter-group comparison was conducted using analysis of variance （ANOVA） and least square deviation-t test. Results The level of hepatocyte CHOP mRNA expression in IGT control group and Ex group was markedly higher than that in NGT group （both P0.05）. 8 weeks after exendin-4 intervention, there was a decline in the expression of CHOP mRNA in NGT and exgroups （both P0.05） as compared with IGT control group. Conclusion Exendin-4 may ameliorate endoplasmic reticulum stress in rat hepatocyte and is protective against the harmful effects of risk factors associated with liver impairment.