利拉鲁肽通过PI3K/Akt/eNOS通路抑制高糖诱导的内皮细胞凋亡

Effect of Liraglutide on High Gglucose-induced Endothelial Cell Apoptosis by PI3K/Akt/eNOS Pathway

目的探讨胰高血糖素样肽1(glucagon-like peptide-1,GLP-1)类似物利拉鲁肽对高糖诱导人脐静脉内皮细胞(human umbilical vein endothelial cells,HUVECs)凋亡的影响及相关机制。方法 HUVECs分组后加入不同处理因素,分别培养24 h;western blot印迹测定细胞磷脂酰肌醇3激酶(phosphoinositide 3-kinase,PI3K),兔抗人磷酸化PI3K(phospheralyted PI3K,p-PI3K),兔抗人蛋白激酶B(protein kinase B,Akt),兔抗人磷酸化Akt(phospheralyted Akt,p-Akt),兔抗人一氧化氮合酶(endothelial nitric oxide synthase,eNOS),兔抗人磷酸化eNOS(phospheralyted eNOS,p-eNOS)表达水平。结果与正糖(5.5 mmol/L)比较,高糖(33 mmol/L)培养24 h后HUVECs凋亡率增加(P<0.05),p-PI3K,p-Akt,p-eNOS表达均下降(P<0.05);高糖条件下加入不同剂量利拉鲁肽培养24 h后,与高糖组比较,细胞凋亡率降低(P<0.05),p-PI3K,p-Akt,p-eNOS表达增加(P<0.05);在高糖+利拉鲁肽组中加入GLP-1受体抑制剂exendin(9-39)(100 nmol/L)后细胞凋亡率和p-PI3K,p-Akt,p-eNOS蛋白表达与高糖组相当(P>0.05)。结论利拉鲁肽可改善高糖诱导的HUVECs凋亡,该抗凋亡作用可能与PI3K/Akt/eNOS通路上调相关且呈GLP-1受体依赖性。

Objective To investigate the effect of glucagon-like peptide-1（GLP-1）on the apoptosis of human umbilical vein endothelial cells（HUVECs）induced by high glucose impact and related mechanisms.Methods The expression of phosphoinositide 3-kinase（PI3K）,phospheralyted PI3K（p-PI3K）,protein kinase B（Akt）,phospheralyted Akt（p-Akt）,endothelial nitric oxide synthase（eNOS）and phospheralyted eNOS（p-eNOS）were detected by western blot after adding different treatment factors for HUVECs.Results The apoptotic rate of HUVECs increased after 24 h of high glucose group（33 mmol/L）,and the levels of p-PI3 K,p-Akt and p-eNOS were decreased when compared with the normal glucose group（P〈0.05）.The levels of p-PI3 K,p-Akt and p-eNOS increased（P〈0.05）when compared with the high glucose group（P〈0.05）.GLP-1 receptor inhibitor exendin（9-39）（100 nmol/L）could block the anti-apoptotic effect of GLP-1 analogue liraglutide and affect the expression of p-PI3 K,p-Akt and p-eNOS protein.Conclusion Liraglutide can improve the apoptosis of HUVECs induced by high glucose,which may be related to the upregulation of PI3K/Akt/eNOS pathway and GLP-1 receptor-dependent.