清心解瘀颗粒调控线粒体自噬对C57B/L6小鼠心肌梗死后心室重构的影响  

Effect of Qingxin Jieyu Granules Regulating Mitophagy on Ventricular Remodeling After Myocardial Infarction of C57B/L6 Mice

作　　者：陈一帆 褚剑锋 姜众会 高铸烨[1] CHEN Yifan;CHU Jianfeng;JIANG Zhonghui;GAO Zhuye(Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing 100091,China;Research Institute of Integrated Chinese and Western Medicine,Fujian University of Traditional Chinese Medicine,Fuzhou 350100,China)

机构地区：[1]中国中医科学院西苑医院,北京100091 [2]福建中医药大学中西医结合研究院,福州350100

出　　处：《中国实验方剂学杂志》2025年第6期70-78,共9页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(82274508,82405168);国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202007);中国中医科学院科技创新工程重大攻关项目(CI2021A00920);中国中医科学院西苑医院中医药临床科研一体化平台建设专项(XYZX0405-10)。

摘　　要：目的:探讨清心解瘀颗粒对于心肌梗死后心室重构小鼠的影响及对线粒体自噬的调控作用。方法:60只雄性C57BL/6小鼠随机分为假手术组,模型组,清心解瘀低、中、高剂量组(1.3、2.6、5.2 g·kg^(-1)),沙库巴曲缬沙坦钠组(0.03 g·kg^(-1)),每组10只,除假手术组外,其余各组均使用冠状动脉左前降支结扎方法建立心肌梗死模型。超声检测小鼠左室舒张末期和收缩末期内径(LVIDd,LVIDs)、左室舒张期和收缩期后壁厚度(LVPWd,LVPWs)、左室舒张末期和收缩末期容积(LV Vold,LV Vols)、左室射血分数(LVEF)、左室短轴缩短率(LVFS);计算小鼠心脏质量指数、心胫比;酶联免疫吸附测定法(ELISA)检测小鼠血清脑纳肽(BNP)、肌酸激酶同工酶(CK-MB)、血管紧张素Ⅱ(AngⅡ)、乳酸脱氢酶(LDH);苏木素-伊红(HE)、马松(Masson)染色观察小鼠心肌组织形态;免疫组化检测小鼠心肌组织血管生成蛋白碱性成纤维细胞生长因子(bFGF)、血管内皮生长因子(VEGF)表达;透射电镜观察小鼠心肌组织线粒体形态;蛋白免疫印迹法(Western blot)检测各组小鼠心肌组织磷酸化腺苷酸活化蛋白激酶(p-AMPK)、磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)蛋白表达。结果:与假手术组比较,模型组小鼠LV Vold、LV Vols、LVIDd、LVIDs、心脏质量指数、心胫比、BNP、LDH、p-mTOR蛋白表达增加(P<0.05),LVPWd、LVPWs、LVEF、LVFS、p-AMPK蛋白表达减少(P<0.05),小鼠心肌细胞有大量炎性细胞浸润并伴有大量胶原沉积,bFGF、VEGF蛋白表达减少,心肌组织线粒体肿胀,嵴碎裂;与模型组比较,沙库巴曲缬沙坦钠组及清心解瘀颗粒中剂量组的LVIDs、LV Vold、LV Vols、BNP、CK-MB、LDH、p-mTOR蛋白表达明显减少(P<0.05),LVEF、LVFS、p-AMPK表达明显增加(P<0.05),各给药组心肌组织炎性细胞浸润及胶原沉积均得到改善,bFGF、VEGF蛋白表达增多,各组小鼠心肌组织线粒体肿胀减轻,出现自噬小体和溶酶体。结论:�Objective:To explore the effects of Qingxin Jieyu granules on ventricular remodeling of mice after myocardial infarction,and their regulatory role in mitophagy.Methods:Sixty male C57BL/6 mice were randomly assigned to six groups:sham-operated group,model group,Qingxin Jieyu granules low-,medium-,and high-dose groups(1.3,2.6,5.2 g·kg^(-1)),and sacubitril valsartan sodium group(0.03 g·kg^(-1)),with 10 mice per group.Except for the sham-operated group,all other groups utilized left anterior descending coronary artery ligation to build a myocardial infarction model.Ultrasound was used to measure left ventricular parameters,including end-diastolic and end-systolic diameters(LVIDd,LVIDs),diastolic and systolic posterior wall thickness(LVPWd,LVPWs),end-diastolic and end-systolic volumes(LV Vold,LV Vols),left ventricular ejection fraction(LVEF),and fractional shortening(LVFS).Additionally,the heart mass index and heart weight/tibia length ratio of mice were calculated.Enzyme-linked immunosorbent assay(ELISA)was employed to quantify brain natriuretic peptide(BNP),creatine kinase isoenzyme(CK-MB),angiotensin Ⅱ(AngⅡ),and lactate dehydrogenase(LDH)levels in the serum of mice.Histological analysis using hematoxylin-eosin(HE)and Masson staining was conducted to examine morphological changes in myocardial tissue.Immunohistochemistry assessed the expression of vascular growth factors,including basic fibroblast growth factor(bFGF)and vascular endothelial growth factor(VEGF).Transmission electron microscopy was used to scrutinize mitochondrial morphology in the myocardial tissue of mice.Western blot was performed to analyze the expression of phosphorylated adenosine monophosphate activated protein kinase(p-AMPK)and phosphorylated mammalian target of rapamycin(p-mTOR)proteins in myocardial tissue from each experimental group.Results:Compared to the sham-operated group,the model group mice exhibited significantly elevated levels of LV Vold,LV Vols,LVIDd,LVIDs,cardiac mass index,heart weight/tibia length ratio,BNP,LDH,and p-mTO

关 键 词：清心解瘀颗粒 心肌梗死 心室重构 心力衰竭 线粒体自噬 

分 类 号：R259[医药卫生—中西医结合] R285[医药卫生—中医内科学] R541[医药卫生—中医学]