芪苈强心胶囊对心肌梗死大鼠心脏IP3Rs/GRP75/VDAC1基因调控的机制研究  

Mechanism of Qiliqiangxin capsule on the regulation of IP3Rs/GRP75/VDAC1 gene in myocardial infarction rat heart

作　　者：纪晓迪 杨丁 崔喜元 娄利霞[1] 聂波[1] 赵久丽 赵明镜[1] 吴爱明[1] JI Xiao-di;YANG Ding;CUI Xi-yuan;LOU Li-xia;NIE Bo;ZHAO Jiu-li;ZHAO Ming-jing;WU Ai-ming(Dongzhimen Hospital of Traditional Chinese Medicine,Ministry of Education and Beijing Key Laboratory of Internal Medicine of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院/中医内科学教育部和北京市重点实验室,北京100700

出　　处：《海南医学院学报》2023年第11期815-824,共10页Journal of Hainan Medical University

基　　金：北京中医药大学东直门医院2022科技创新专项(DZMKJCX⁃2022⁃008)。

摘　　要：目的:探讨芪苈强心胶囊对心肌梗死大鼠线粒体Ca^(2+)转运相关基因的调控作用。方法:采用冠状动脉左前降支结扎术建立心肌梗死大鼠模型。术后随机将动物分到模型组、芪苈强心组和卡托普利组;同时设有假手术组作为对照。治疗四周后,通过心脏大体结构观察大鼠心脏梗死范围,HE染色观察大鼠心肌组织病理形态变化;实时荧光(Real⁃Time)PCR检测大鼠心脏梗死边缘区线粒体Ca^(2+)转运相关基因三磷酸肌醇受体2(IP3R2),葡萄糖调节蛋白75(GRP75),电压依赖性阴离子通道1(VDAC1),线粒体融合蛋白2(Mfn2),以及线粒体凋亡相关基因B淋巴细胞瘤⁃2(Bcl⁃2),Bcl⁃2相关X蛋白(Bax)mRNA表达变化;Western blot检测心肌组织Bcl⁃2,Bax蛋白表达变化;TUNEL染色检测心肌组织细胞凋亡率。结果:与假手术组相比,模型组大鼠心脏左室前壁呈现大面积梗死区域,心肌组织结构紊乱;线粒体Ca^(2+)转运相关基因IP3R2,GRP75,VDAC1,Mfn2 mRNA表达显著升高(P<0.05,P<0.01);线粒体凋亡相关分子Bcl⁃2 mRNA和蛋白表达均明显下降(P<0.01),Bax mRNA和蛋白表达均显著升高(P<0.01),心肌细胞凋亡率显著增加(P<0.01)。与模型组相比,芪苈强心组和卡托普利组心脏大体标本的梗死范围缩小,心肌纤维排列相对规整;线粒体Ca^(2+)转运相关基因IP3R2,GRP75,VDAC1,Mfn2 mRNA表达显著降低(P<0.01);线粒体凋亡相关分子Bcl⁃2 mRNA和蛋白表达有所提高(P<0.05,P<0.01),Bax mRNA和蛋白表达显著降低(P<0.05,P<0.01),心肌细胞凋亡率明显下降(P<0.01)。结论:芪苈强心胶囊能够改善心肌梗死大鼠心脏形态结构,其作用机制与调节线粒体Ca^(2+)转运复合体IP3R2/GRP75/VDAC1基因表达,进而抑制细胞凋亡有关。Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left anterior descending coro⁃nary artery.After operation,the rats were randomly assigned to the model group,the Qiliqiangxin group and the captopril group;a sham⁃operated group was also available as a control.After four weeks of treatment,the extent of infarction in rats was observed by gross cardiac structure and the morphological changes of myocardial histopathology were observed by HE staining.Detection of mitochondrial Ca^(2+) transport⁃related genes such as inositol⁃1,4,5⁃trisphosphate receptor 2(IP3R2),glucose regulated protein 75(GRP75),voltage⁃dependent anion channel 1(VDAC1),and mitofusion 2(Mfn2)and mitochondrial apoptosis⁃related genes such as B⁃cell lymphoma⁃2(Bcl⁃2)and Bcl⁃2 related X protein(Bax)mRNA expression changes was measured by RT⁃PCR in the infarct margins of the heart;Western blot was used to detect changes in Bcl⁃2,Bax protein expression in myocardial tissue.The rate of apoptosis in cardiac myocardial tissue was detected by TUNEL staining.Results:Compared with the sham group,the anterior left ventricular wall of the model group showed a large area of infarction,and the structure of myocardial tissue was disor⁃dered.The mRNA expression level of mitochondrial Ca^(2+)transport⁃related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly increased(P<0.05,P<0.01);The mRNA and protein expression of Bcl⁃2,a molecule related to mitochondri⁃al apoptosis,were significantly decreased(P<0.01),while the mRNA and protein expression of Bax were significantly increased(P<0.01);and apoptosis rate was significantly increased(P<0.01).Compared with the model group,the infarct size of cardiac gross specimens in the Qiliqiangxin group and the captopril group was reduced and myocardial fibers were relatively well ordered;The mRNA expression of mitochondrial Ca^(2+

关 键 词：心肌梗死 芪苈强心胶囊 Ca^(2+)转运 IP3Rs/GRP75/VDAC1复合体 

分 类 号：R285.5[医药卫生—中药学]