基于线粒体凋亡通路探讨红参、黄芪及其配伍对心力衰竭大鼠的干预机制  

Mechanism of Red Ginseng,Astragalus Membranaceus and their compatibility on heart failure in rats via mitochondrial apoptosis pathway

作　　者：温玉 李欧[2] 胡琨建 董桦[1] WEN Yu;LI Ou;HU Kunjian;DONG Hua(The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300381,China;The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300143,China;Guiyang Fourth People’s Hospital,Guiyang 550002,Guizhou,China)

机构地区：[1]天津中医药大学第一附属医院,天津300381 [2]天津中医药大学第二附属医院,天津300143 [3]贵阳市第四人民医院,贵州贵阳550002

出　　处：《现代中西医结合杂志》2025年第6期731-738,共8页Modern Journal of Integrated Traditional Chinese and Western Medicine

基　　金：天津市教委科研计划项目(2019KJ052);国家重点研发计划课题(2019YFC1710005)。

摘　　要：目的探讨红参、黄芪及其配伍的水煎液对心力衰竭大鼠的干预作用及对线粒体凋亡通路的影响。方法取雄性SD大鼠80只,随机选取10只作为假手术组,其余70只大鼠采用腹主动脉缩窄法建立心力衰竭模型。将术后12周证实造模成功的40只大鼠按照体重随机分为模型组、红参组、黄芪组、红参+黄芪组、曲美他嗪组,每组8只。红参组、黄芪组、红参+黄芪组大鼠分别给予红参0.84 g/(kg·d)、黄芪4.16 g/(kg·d)、红参+黄芪5 g/(kg·d)灌胃,曲美他嗪组大鼠给予曲美他嗪6.25 mg/(kg·d)灌胃,模型组及假手术组大鼠给予相同体积的生理盐水灌胃,均1次/d,连续灌胃8周。灌胃结束后,心脏超声检测心功能,HE染色观察心肌组织病理形态,透射电镜观察心肌细胞超微结构,TUNEL染色检测心肌细胞凋亡情况,Western blot法检测心肌组织中电压依赖性阴离子通道蛋白1(VDAC1)、细胞色素C(Cyt-C)、B细胞白血病/淋巴瘤2(Bcl-2)、Bcl2关联X蛋白(Bax)、半胱氨酸蛋白酶-3(Caspase-3)蛋白表达情况。结果与假手术组比较,模型组大鼠心室扩张,室壁运动减弱,LVEF、LVFS均明显降低(P均<0.05);心肌细胞排列不规整,有大量肥大的心肌细胞,部分炎性细胞浸润,心肌组织内存在少量成纤维细胞;心肌细胞超微结构异常,线粒体排列紊乱,嵴溶解,基质较少,可见自噬小体;心肌细胞凋亡率和心肌组织中VDAC1、Cyt-C、Bax、Caspase-3蛋白相对表达量均明显升高(P均<0.05),心肌组织中Bcl-2蛋白相对表达量明显降低(P<0.05)。与模型组比较,各给药组大鼠的心腔扩张程度减轻,室壁运动增强,LVEF、LVFS均明显升高(P均<0.05);心肌细胞损伤程度减轻,线粒体结构基本正常;黄芪组、红参+黄芪组、曲美他嗪组大鼠心肌细胞凋亡率和各给药组大鼠心肌组织中VDAC1、Cyt-C、Bax、Caspase-3蛋白相对表达量均明显降低(P均<0.05),红参+黄芪组和曲美他嗪组大鼠心肌组织中Bcl-2Objective It is to explore the intervention effect of decoctions of Red Ginseng(RG),Astragalus Membranaceus(AM)and their compatibility on heart failure in rats,and to explore its effect on mitochondrial apoptosis pathway.Methods Eighty male SD rats were taken,10 of which were randomly selected as the sham operation group,and the remaining 70 rats were used to establish models of heart failure by abdominal aortic constriction method.40 successfully modeled rats confirmed at 12 weeks after the operation were randomly divided into model group,RG group,AM group,RG+AM group and trimetazidine group according to their body weights,with 8 rats in each group.The rats in the RG group,AM group and RG+AM group were respectively given RG 0.84 g/(kg·d),AM 4.16 g/(kg·d)and RG+AM 5 g/(kg·d)by gavage,the rats in the trimetazidine group were given trimetazidine 6.25 mg/(kg·d)by gavage,and the rats in the model group and sham operation group were given the same volume of saline by gavage,all once daily,continuously gavaged for 8 weeks.At the end of gavage,the cardiac function was detected by cardiac ultrasound,the pathological morphology of myocardial tissue was observed by HE staining,the ultrastructure of myocytes was observed by transmission electron microscopy,the apoptosis of myocytes was detected by TUNEL staining,and the protein expressions of voltage-dependent anion channel 1(VDAC1),cytochrome C(Cyt-C),Bcl-2,Bax and Caspase-3 in myocardial tissues were detected by Western blot.Results Compared with the sham operation group,the ventricles of rats in the model group were dilated and their ventricular wall motion was weakened,their LVEF and LVFS were significantly decreased(all P<0.05);the cardiomyocytes were irregularly arranged,with a large number of hypertrophic cardiomyocytes,partially infiltrated by inflammatory cells,and a small number of fibroblasts existed in the cardiac myocyte tissues;cardiomyocyte ultrastructure was abnormal,with disordered arrangement of mitochondria,lysed cristae,fewer substrates and visible a

关 键 词：心力衰竭 红参 黄芪 线粒体凋亡 

分 类 号：R-332[医药卫生]