摘要
目的分析缺血后处理(ischemic postconditioning,IP)对心肌缺血再灌注(ischemia-reperfusion,IR)大鼠心功能、心肌细胞凋亡和心肌组织线粒体凋亡相关分子表达的影响。方法将40只8周龄雄性SD大鼠分笼喂养,每笼5只,适应性饲养7 d,随机分为空白对照组(对照组)、假手术组(S组)、心肌IR造模组(IR组)、心肌IP造模+IP处理组(IP组),每组各10只。术后4 h使用生物机能实验系统记录大鼠心功能[左心室收缩压(left ventricular systolic pressure,LVSP)、心室舒张末压(left ventricular enddiastolic pressure,LVEDP)、左心室压变化速率最大值(±dp/dtmax)]。采用TUNEL法检测心肌细胞凋亡指数,采用RT-PCR法检测心肌细胞凋亡相关蛋白BCL-2、BAX及天冬氨酸特异性半胱氨酸蛋白酶-3(cysteinylaspartate-specific proteinase 3,Caspase-3)、法尼酯衍生物X受体(farnesyl X receptor,FXR)、小异二聚体配体(small heterodimer partner,SHP)相对表达量。蛋白质印迹法检测心肌细胞线粒体凋亡通路标志物细胞色素C(cytochrome C,Cyt-C)的释放量。结果IP组及IR组LVEDP、心肌细胞凋亡指数、心肌组织BAX、CASPASE-3、FXR、SHP相对表达量及心肌细胞胞浆Cyt-C蛋白灰度值均高于S组、对照组(P<0.05),IR组LVEDP、心肌细胞凋亡指数、BAX、CASPASE-3、FXR、SHP相对表达量及Cyt-C蛋白灰度值高于IP组(P<0.05);IP组及IR组LVSP、±dp/dtmax、心肌组织BCL-2相对表达量均低于S组、对照组(P<0.05),IR组LVSP、±dp/dtmax、心肌组织BCL-2相对表达量均低于IP组(P<0.05)。结论IP处理可减轻大鼠心肌IR损伤,改善心功能,可能与调控BCL-2/BAX、FXR/SHP等凋亡相关信号蛋白的表达有关。
Objective To analyze the influence of ischemic postconditioning(IP)on cardiac function,myocardial apoptosis and expressions of myocardial tissue mitochondrial apoptosis-related molecules in rats with myocardial ischemia-reperfusion(IR).Methods Forty 8-week-old male SD rats were fed in separate cages with 5 rats in each cage for 7 days of adaptive feeding,and were randomly divided into 4 groups:blank control group(control group),sham operation group(S group),myocardial IR model group(IR group)and myocardial IR model+IP treatment group(IP group),with 10 rats in each group.At 4 hours after surgery,the cardiac function indicators[left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),maximum rate of left ventricular pressure change(±dp/dtmax)]were recorded by biological functional system,and the apoptosis of myocardial cells was detected by TUNEL method.RT-PCR was used to detect the relative expression levels of myocardial apoptosis-related proteins BCL-2,BAX,cysteinyl aspartate specific protease-3(Caspase-3),farnesoid X receptor(FXR)and small heterodimer partner(SHP).Western blotting was applied to detect the release of myocardial mitochondrial apoptosis pathway marker cytochrome C(Cyt-C).Results The LVEDP,apoptosis index of myocardial cells,and the expression levels of BAX,CASPASE-3,FXR and SHP in myocardial tissues and the expression level of Cyt-C protein in myocardial cytoplasm were higher in the IP and IR groups than those in the S and control groups(P<0.05),moreover,the above indicators in the IR group were higher than those in the IP group(P<0.05).The LVSP,±dp/dtmax and the expression level of BCL-2 in myocardial tissues in the IP group and IR group were lower than those in the S group and control group(P<0.05),and the above indicators were lower in the IR group than those in the IP group(P<0.05).Conclusion IP treatment can alleviate the myocardial IR injury and improve the cardiac function in rats,which may be related to the regulations of apoptosisrelated signal proteins such as BCL-2/BAX and FXR/SHP.
作者
王涛
郝恩刚
WANG Tao;HAO Engang(Department of Cardiovascular Medicine,the Second People’s Hospital of Liaocheng,Liaocheng,Shandong,252600,China)
出处
《医学分子生物学杂志》
CAS
2024年第6期586-590,596,共6页
Journal of Medical Molecular Biology
关键词
心肌缺血再灌注
缺血后处理
心肌细胞凋亡
心肌细胞线粒体凋亡
心功能
myocardial ischemia-reperfusion
ischemic postconditioning
myocardial apoptosis
myocardial mitochondrial apoptosis
cardiac function
