利拉鲁肽激活Akt通路改善乳鼠心肌细胞缺氧/复氧损伤

摘要

目的:研究利拉鲁肽对乳鼠心肌细胞缺氧/复氧损伤的影响及机制.方法:分离乳鼠心肌细胞,分为对照组、缺氧/复氧组和利拉鲁肽组,体外构建缺氧/复氧损伤模型,使用流式细胞术检测细胞凋亡情况,Western blot检测凋亡相关蛋白caspase-3、Akt以及Akt磷酸化水平.结果:对乳鼠心肌细胞进行缺氧/复氧损伤处理后,流式细胞术检测发现,与对照组相比,缺氧/复氧损伤能明显诱导细胞凋亡,而利拉鲁肽则有抗凋亡作用;Western blot结果提示,缺氧/复氧损伤可诱导caspase-3表达,激活凋亡相关信号通路,促进细胞凋亡,而利拉鲁肽组细胞Akt磷酸化水平明显增加,caspase-3表达减少、活性降低.结论:利拉鲁肽可以通过增加Akt磷酸化以激活Akt通路,抑制caspase-3的表达,发挥抗凋亡作用,改善缺氧/复氧损伤.%Objective:To study the effects of liraglutide on hypoxia/reoxygenation injury in neonatal rat cardio-myocytes and the underlying mechanism .Methods:The cardiomyocytes were isolated from neonatal rats , and then divided into control group , hypoxia /reoxygenation group and liraglutide group .The model of hypoxia /reoxygen-ation injury was established in vitro.Apoptosis was detected by flow cytometry and apoptosis related proteins inclu-ding caspase-3, Akt, and phospho-Akt were detected by Western blot .Results: Cardiomyocytes of neonatal rats were treated with hypoxia /reoxygenation injury , compared with the control group , results of flow cytometry showed that hypoxia /reoxygenation injury could induce apoptosis of neonatal rat cardiomyocytes , while liraglutide had anti-apoptosis effects .Western blot showed that the expression of caspase-3 was activated by the hypoxia /reoxygenation injury.While in the liraglutide group, the phosphorylation of Akt was increased , as a result, the expression and ac-tivation of caspase-3 was suppressed .Conlusion:Liraglutide could improve the hypoxia/reoxygenation injury by in-creasing Akt phosphorylation to activate the Akt pathway , suppress the expression of caspase-3, and harbour an an-ti-apoptotic effect .