洛伐他汀通过调控Akt通路对缺氧/复氧心肌细胞损伤的保护作用  

Protective effects of lovastatin on hypoxia/reoxygenation cardiomyocyte injury by regulating Akt pathway

作　　者：韩小虎[1] 腾丽峰 吴清柳[2] 李儒正[1] HAN Xiao-hu;TENG Li-feng;WU Qing-liu;LI Ru-zheng(Department of Cardiac Surgery,Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University,Haikou 570311,Hainan Province,China;Department of Cardiovascular,Hainan General Hospital/Hainan Affiliated Hospital of Hainan Medical University,Haikou 570311,Hainan Province,China)

机构地区：[1]海南省人民医院/海南医学院附属海南医院心脏外科,海南海口570311 [2]海南省人民医院/海南医学院附属海南医院心血管内科,海南海口570311

出　　处：《中国临床药理学杂志》2024年第19期2826-2830,共5页The Chinese Journal of Clinical Pharmacology

基　　金：海南省自然科学基金资助项目(MS0828)。

摘　　要：目的探索洛伐他汀对缺氧/复氧诱导的心肌细胞损伤的保护作用,及其对蛋白激酶B(Akt)信号通路的调控作用。方法体外培养大鼠心肌细胞H9c2,并分为对照组、模型组、抑制组、联合组和低、中、高剂量实验组。对照组给予正常培养液常规培养,其他6组均进行缺氧/复氧处理。低、中、高剂量实验组分别添加1、2和5μmol·L^(-1)洛伐他汀;抑制组添加1μmol·L^(-1)LY294002;联合组添加5μmol·L^(-1)洛伐他汀和1μmol·L^(-1)LY294002。用噻唑蓝法检测细胞活力,用流式细胞仪检测细胞凋亡情况,用蛋白质印迹法检测磷酸化Akt(p-Akt)的表达水平。结果高剂量实验组、抑制组、联合组、模型组和对照组的细胞活力分别为(64.38±7.10)%、(21.64±1.32)%、(51.89±2.25)%、(47.18±6.66)%和(100.00±7.69)%,细胞凋亡率分别为(13.67±1.42)%、(38.52±2.42)%、(21.12±2.27)%、(20.42±3.33)%和(4.93±0.40)%,p-Akt蛋白相对表达水平分别为0.54±0.04、0.04±0.01、0.25±0.03、0.20±0.01和0.45±0.02。高剂量实验组的上述指标与模型组比较,联合组的上述指标与高剂量实验组和抑制组比较,在统计学上差异均有统计学意义(均P<0.05)。结论洛伐他汀能够通过激活Akt信号通路对缺氧/复氧心肌细胞损伤起到保护作用。Objective To investigate the protective effect of lovastatin on cardiomyocyte injury induced by hypoxia/reoxygenation and the regulation of protein kinase B(Akt)signal pathway.Methods Rat cardiomyocytes H9c2 were cultured in vitro,and divided into control group,model group,inhibitor group,combined group and experimentalL,-M,-H groups.Control group was cultured with normal medium,and the other 6 groups were treated with hypoxia/reoxygenation.Experimental-L,-M,-H groups were supplemented with 1,2 and5μmol·L^(-1)lovastatin,respectively;inhibitor group was supplemented with 1μmol·L^(-1)LY294002;combined group was supplemented with5μmol·L^(-1)lovastatin and 1μmol·L^(-1)LY294002.The cell viability was determined by thiazole blue assay,the apoptosis rate was determined by flow cytometry,and the expression level of phosphorylated Akt(p-Akt)was determined by Western blot.Results The cell viabilities of experimental-H,inhibitor,combined,model and control groups were(64.38±7.10)%,(21.64±1.32)%,(51.89±2.25)%,(47.18±6.66)%and(100.00±7.69)%;the cell apoptosis rates were(13.67±1.42)%,(38.52±2.42)%,(21.12±2.27)%,(20.42±3.33)%and(4.93±0.40)%;the relative protein expression levels of p-Akt were 0.54±0.04,0.04±0.01,0.25±0.03,0.20±0.01 and 0.45±0.02,respectively.The differences of above indicators were statistically significant between the experimental-H group and the model group,as well as between the combined group and the experimental-H and inhibitor groups(all P<0.05).Conclusion Lovastatin can protect against hypoxia/reoxygenation cardiomyocyte injury by activating the Akt signaling pathway.

关 键 词：洛伐他汀 大鼠心肌细胞H9c2 缺氧/复氧 磷脂酰肌醇-3-激酶信号通路 

分 类 号：R972[医药卫生—药品]