GLP-1激动剂通过PI3K/Akt信号通路减轻心肌细胞缺氧复氧损伤的实验研究  

GLP-1 agonist protects myocardial hypoxia-reoxygenation injury through PI3K/Akt signaling pathway： anexperimental study

作　　者：易志刚[1] 陈津瀚[1] 李津[1] 郭文安[1] 吴娟[1] 黄上萌[1] 

机构地区：[1]厦门大学附属第一医院干部保健病房,361003

出　　处：《中华内分泌代谢杂志》2018年第1期61-66,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：福建省卫生厅青年科研课题(2013-2-87)

摘　　要：目的研究胰升糖素样肽1（GLP-1）激动剂对心肌细胞缺氧复氧损伤的影响及具体的分子机制。 方法将H9C2细胞株分为对照组、缺氧复氧（H/R）组、H/R＋GLP-1组、H/R＋GLP-1＋磷脂酰肌醇3-激酶（PI3K）抑制剂LY294002组。检测细胞增殖活力、细胞凋亡率、培养基中心肌酶含量以及凋亡相关基因的表达量。建立心肌缺血再灌注损伤（I/R）的动物模型，给予GLP-1激动剂、PI3K抑制剂干预并检测血清中心肌酶的含量。 结果H/R显著降低心肌细胞的增殖活力以及细胞中磷酸化PI3K、磷酸化蛋白激酶B（Akt）、Bcl-2的蛋白表达量，增加细胞凋亡率、细胞培养基中肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）、乳酸脱氢酶（LDH）的含量以及细胞中Bax、Caspase-3的蛋白表达量，而这可被GLP-1所改善（均P〈0.05）；H/R＋GLP-1＋LY294002组心肌细胞的增殖活力以及细胞中Bcl-2的蛋白表达量显著低于H/R＋GLP-1组，细胞凋亡率、细胞培养基中CK、CK-MB、LDH的含量以及细胞中Bax、Caspase-3的蛋白表达量显著高于H/R＋GLP-1组（均P〈0.05）。I/R组大鼠血清CK、CK-MB、LDH含量显著高于对照组和I/R＋GLP-1组，I/R＋GLP-1＋LY294002组大鼠血清中CK、CK-MB、LDH的含量显著高于I/R＋GLP-1组（均P〈0.05）。 结论GLP-1激动剂能够通过激活PI3K/Akt信号通路来减轻心肌细胞缺氧复氧损伤。ObjectiveTo investigate the effects of glucagon like peptide 1（GLP-1）agonist on myocardial hypoxia reoxygenation injury and its molecular mechanism. MethodsH9C2 cells were divided into control group, hypoxia reoxygenation（H/R）group, H/R＋ GLP-1 group, and H/R＋ GLP-1＋ phosphatidylinositol-3-kinase （PI3K） inhibitor LY294002 group. The cell proliferation activity, apoptosis rate, enzyme contents in the medium and the expressions of apoptosis-related genes were detected. After animal model of myocardial ischemia reperfusion injury（I/R）was established and was treated with GLP-1 agonist and PI3K inhibitor, serum enzyme contents were detected. ResultsHypoxia reoxygenation decreased the myocardial cell proliferation activity and phosphorylated-PI3K（p-PI3K）, phosphorylated-protein kinase B（p-Akt）, Bcl-2 protein expressions, increased the apoptotic cell number and creatine kinase（CK）, creatine kinase-MB（CK-MB）, lactate dehydrogenase（LDH）contents in cell culture medium and Bax, caspase-3 protein expressions, which were ameliorated by GLP-1（all P〈0.05）. The myocardial cell proliferation activity and Bcl-2 protein expression of H/R＋ GLP-1＋ LY294002 group were significantly lower than those of H/R＋ GLP-1 group while the apoptotic cell number and CK, CK-MB, LDH contents in cell culture medium and Bax, Caspase-3 protein expressions were significantly higher（all P〈0.05）. Serum CK, CK-MB, and LDH contents in rats of I/R group were significantly higher than those in control group and I/R＋ GLP-1 group. Serum CK, CK-MB, and LDH contents in rats of I/R＋ GLP-1＋ LY294002 group were significantly higher than those in I/R＋ GLP-1 group（all P〈0.05）. ConclusionGLP-1 agonist is able to protect the myocardial hypoxia reoxygenation injury via activating PI3K/Akt signaling pathway.

关 键 词：心肌缺血再灌注损伤 缺氧复氧 胰升糖素样肽1 磷脂酰肌醇3-激酶/蛋白激酶B 

分 类 号：R542.2[医药卫生—心血管疾病]