阿托伐他汀预处理对缺氧复氧后乳鼠心肌细胞的保护作用及其机制  

Protective effect and mechanism of atorvastatin pretreatment on neonatal mouse cardiomyocytes after hypoxia reoxygenation

作　　者：刘会[1] 谭洪文 庞军 张曙影[2] LIU Hui;TAN Hongwen;PANG Jun;ZHANG Shuying(Department of Cardiology,Guizhou Provincial People's Hospital,Guiyang 550002,China;不详)

机构地区：[1]贵州省人民医院心内科,贵阳550002 [2]大连大学附属中山医院心内科

出　　处：《山东医药》2023年第23期34-38,共5页Shandong Medical Journal

基　　金：贵州省人民医院青年基金项目[GZSYQN(2018)06]。

摘　　要：目的探讨阿托伐他汀预处理对缺氧复氧后乳鼠心肌细胞的保护作用是否与线粒体ATP敏感的钾通道(mitoKATPC)和线粒体膜通透性转换孔(MPTP)有关。方法将原代培养的C57BL/6乳鼠心肌细胞随机分为五组,control组常规培养,H/R组、Ator组、5-HD+Ator组和LND+Ator组均进行缺氧复氧处理(缺氧12 h、复氧6 h);Ator组缺氧复氧前给予1μmol/L阿托伐他汀预处理3 h,5-HD+Ator组缺氧复氧前给予100μmol/L mitoK_(ATP)C通道阻断剂5-羟基葵酸+1μmol/L阿托伐他汀干预3 h,LND+Ator组缺氧复氧前给予1μmol/L阿托伐他汀干预3 h+30μmol/L MPTP开放剂氯尼达明干预20 min。采用CCK-8法检测细胞存活率,流式细胞术检测细胞内钙离子浓度、线粒体膜电位、MPTP开放情况和活性氧(ROS)含量。结果与control组比较,H/R组、Ator组、5-HD+Ator组、LND+Ator组细胞存活率均降低、钙离子浓度均升高,H/R组、5-HD+Ator组、LND+Ator组线粒体膜电位均降低、MPTP开放程度及ROS含量均升高(P均<0.05)。与H/R组、5-HD+Ator组、LND+Ator组比较,Ator组细胞存活率、线粒体膜电位均升高,钙离子浓度、MPTP开放程度及ROS含量均降低(P均<0.05)。结论阿托伐他汀对缺氧复氧后的乳鼠心肌细胞具有保护作用,其机制可能与开放mitoK_(ATP)C和关闭MPTP从而抑制ROS生成有关。Objective To investigate whether the protective effect of atorvastatin preconditioning on neonatal mouse cardiomyocytes after hypoxia reoxygenation is related to mitochondrial ATP-sensitive potassium channel(mitoK_(ATP)C)and mitochondrial permeability transition pore(MPTP).Methods The primary cultured C57BL/6 mouse cardiomyocytes were randomly divided into five groups.The cardiomyocytes in the control group underwent routine culture,while the car⁃diomyocytes in the H/R group,Ator group,5-HD+Ator group,and LND+Ator group were all subjected to hypoxia and re⁃oxygenation treatment(hypoxia for 12 h,reoxygenation for 6 h).In the Ator group,1μmol/L atorvastatin pretreatment for 3 h before anoxic reoxygenation treatment;in the 5-HD+Ator group,the cardiomyocytes were given 100μmol/L 5-hy⁃droxysunflower acid and 1μmol/L atorvastatin intervention for 3 h before hypoxia reoxygenation;in the LND+Ator group,the cardiomyocytes were given 1μmol/L atorvastatin intervention of 3 h and 30μmol/L lonidamine intervention of 20 min⁃utes.CCK-8 method was used to detect the cell survival rate,and flow cytometry was used to detect the intracellular calci⁃um concentration,mitochondrial membrane potential,MPTP opening,and the content of reactive oxygen species(ROS).Results Compared with the control group,the cell survival rates of the H/R group,Ator group,5-HD+Ator group,LND+Ator group significantly decreased,and the concentration of calcium ions significantly increased,the mitochondrial membrane potential of the H/R group,5-HD+Ator group,and LND+Ator group significantly decreased,and the opening degree of MPTP and the content of ROS significantly increased(all P<0.05).Compared with the H/R group,5-HD+Ator group and LND+Ator group,the cell survival rate and mitochondrial membrane potential in the Ator group significantly increased,and the calcium concentration,MPTP opening degree and ROS content significantly decreased(all P<0.05).Conclusion Atorvastatin has protective effect on neonatal mouse cardiomyocytes after hypoxia re

关 键 词：阿托伐他汀 线粒体ATP敏感的钾通道 线粒体膜通透性转换孔 心肌细胞 缺氧复氧损伤 

分 类 号：R542.2[医药卫生—心血管疾病]