Liraglutide及PTEN在高脂饮食诱导的大鼠胰岛细胞凋亡中的作用

目的观察高脂饮食的SD大鼠胰腺第10号染色体同源丢失性磷酸酶-张力蛋白基因（PTEN）表达量的变化，以及liraglutide对胰岛细胞凋亡的作用。方法20只雄性SD大鼠随机分为3组：正常饮食（ND）组（n=6）、高脂饮食（HFD）组（n=6）和高脂饮食并给予liraglutide（HL）组（n=8）。ND组给予正常饮食，HFD组和HL组给予高脂饮食持续20周后行0GTT试验。随后ND组和HFD组给予生理盐水0．2mg／kg，HL组给予liraglutide0．2mg／kg，早晚各1次，持续4周，给药终点再次行OG-TT试验，评估β细胞功能。应用实时定量PCR检测各组大鼠胰腺PTENmRNA相对表达量，TUNEL染色观察大鼠胰岛细胞凋亡的变化。结果与ND组相比，HFD组和HL组大鼠体重增加（P〈0．05），血TG和TC升高（P〈0．01），OGTT中胰岛素曲线下面积（AUCIns）增大（P〈0．05或P〈0．01），且胰腺PTENmRNA表达量增多（P〈0．05）。与HFD组相比，HL组体重、进食量和血TC下降（P〈0．05或P〈0．01），OGTT中60min和120min时胰岛素和血糖降低（P〈O．01），胰岛细胞凋亡减少，β细胞功能得到一定改善，但胰腺PTENmRNA表达量的差异无统计学意义（P〉0．05）。结论高脂饮食时SD大鼠胰腺PTENmRNA表达增加，liraglutide对高脂饮食大鼠胰腺PTENmRNA表达没有影响，但可能通过Akt信号通路减少其胰岛细胞凋亡。

Effect of liraglutide and PTEN on rats pancreatic islet cell apoptosis induced by high fat diet

Objective To investigate the expression of phosphatase and tensin homologue （PTEN） deleted on chromosome ten in pancreas of high fat diet rats and the effect of liraglutide on pancreatic islet cell apoptosis. Method Twenty male SD rats were divided into three groups at random： normal diet （ND,n= 6）, high fat diet （HFD, n= 6） and high fat diet with liraglutide（HL, n= 8）. They were given corresponding food for 20 weeks respectively, followed by an OGTT. Then, the three groups were subjected to subcutaneous administration of saline, saline and liraglutide respectively, 0. 2 mg/kg, twice a day（08：00 and 20：00） for 4 weeks. Amount of food intake was recorded every day and body weight was monitored once every three days. At the end point of administration, another OGTT was done to estimate the function of β cell in each group. The mRNA level of PTEN in pancreas was detected through RT-PCR. Pancreatic sections were stained with TUNEL to test pancreatic islet cell apoptosis. Results Compared with ND group, the rats in HFD and HL groups obtained more body weight and higher levels of triglyceride, total cholesterol and pancreatic PTEN mRNA. Also, they showed bigger value of INS-AUC （Area under curve of insulin） during OGTT. Compared with HFD group, sustained administration for 4 weeks with liraglutide in HL rats decreased total cholesterol（P〈0. 05）, food intake（P〈0. 01）, body weight（P〈0. 05） and pancreatic islet cell apoptosis and improved their β cell function. The levels of blood glucose（P〈0. 01） and serum insulin（P〈0. 01） were lower in HL group than in HFD group at 60min and 120min during OGTT at the end point of administration. No significant difference was seen in pancreatic PTEN mRNA between this two groups. Conclusions Pancreatic PTEN mRNA is upregulated in high fat diet rats. Liraglutide may protect pancreatic islet cell in high fat diet rats against apoptosis through Akt signalling pathway with no effect on pancreatic PTEN mRNA.