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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OGTT试验。随后ND组和HFD组给予生理盐水0.2 mg/kg,HL组给予liraglutide 0.2 mg/kg,早晚各1次,持续4周,给药终点再次行OGTT试验,评估β细胞功能。应用实时定量PCR检测各组大鼠胰腺PTEN mRNA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(AUC_(Ins))增大(P<0.05或P<0.01),且胰腺PTEN mRNA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60 min和120 min时胰岛素和血糖降低(P<0.01),胰岛细胞凋亡减少,β细胞功能得到一定改善,但胰腺PTEN mRNA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PTEN mRNA表达增加,liraglutide对高脂饮食大鼠胰腺PTEN mRNA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。
Objective To observe the change of PTEN gene expression on chromosome 10 in the pancreas of high fat diet and the effect of liraglutide on islet cell apoptosis. Methods Twenty male Sprague-Dawley rats were randomly divided into 3 groups: normal diet group (n = 6), high fat diet group (n = 6) and high fat diet group and given liraglutide = 8). ND group was given normal diet, HFD group and HL group were given high-fat diet for 20 weeks after OGTT test. Subsequently, 0.2 mg / kg of saline was given to ND and HFD groups, and 0.2 mg / kg of liraglutide was given to HL group. The HL group was given once a morning and one night for 4 weeks. OGTT was performed again at the end of administration to evaluate the function of β cells. The relative expression of PTEN mRNA in pancreas of each group was detected by real-time quantitative PCR. The apoptosis of islet cells was observed by TUNEL staining. Results Compared with ND group, body weight of HFD group and HL group increased (P <0.05), blood TG and TC increased (P <0.01), and area under insulin curve (AUC - Ins) in OGTT increased <0.05 or P <0.01), and the expression of PTEN mRNA in pancreas increased (P <0.05). Compared with HFD group, body weight, food intake and blood TC decreased (P <0.05 or P <0.01) in HL group, while insulin and blood glucose decreased at 60 min and 120 min in OGTT (P <0.01) β cell function was improved, but there was no significant difference in the expression of PTEN mRNA in pancreas (P> 0.05). Conclusion The expression of PTEN mRNA in the pancreas of SD rats increased during high-fat diet, and liraglutide had no effect on the expression of PTEN mRNA in the pancreas of high-fat diet rats, but it may reduce the apoptosis of pancreatic islets through the Akt signaling pathway.