升陷汤对慢性心力衰竭大鼠心肌微血管损伤的保护作用  

Protective Effect of Shengxiantang on Myocardial Microvascular Injury in Rats with Chronic Heart Failure

作　　者：高卉 杨泽祺 高凡 李红京 陆艾阳子 刘兴超 郭秋红 GAO Hui;YANG Zeqi;GAO Fan;LI Hongjing;LU Aiyangzi;LIU Xingchao;GUO Qiuhong(Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Hebei Provincial Hospital of Traditional Chinese Medicine(TCM),Shijiazhuang 050032,China;Hebei Technology Innovation Center for TCM Formula Preparations,Shijiazhuang 050200,China;Hebei Higher Education Institute Applied Technology Research Center for TCM Development and Industrialization,Shijiazhuang 050200,China)

机构地区：[1]河北中医药大学,石家庄050200 [2]河北省中医院,石家庄050032 [3]河北省中药组方制剂技术创新中心,石家庄050200 [4]河北省高校中药开发与产业化应用技术研发中心,石家庄050200

出　　处：《中国实验方剂学杂志》2025年第7期35-42,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：河北省自然科学基金项目(H2023423075);河北省中医药管理局科研计划项目(2023111)。

摘　　要：目的:探讨升陷汤对慢性心力衰竭(CHF)大鼠心功能及心肌微血管损伤的保护作用。方法:采用主动脉弓缩窄术(TAC)制备CHF大鼠模型,72只SD大鼠随机选取8只为假手术组,只开胸不结扎主动脉弓,将造模成功的40只大鼠随机分为模型组,升陷汤低、中、高剂量组(5.1、10.2、20.4 g·kg^(-1)),盐酸曲美他嗪组(6.3 mg·kg^(-1)),每组各8只。造模后4周开始给药,给药组分别予相应药物灌胃,假手术组和模型组予等量蒸馏水,连续给药8周。超声心动图检测大鼠心功能;酶联免疫吸附测定法(ELISA)检测一氧化氮(NO)、内皮素(ET-1)、血管内皮生长因子(VEGF)、血管性血友病因子(vWF)水平;透射电镜观察微血管超微结构变化;免疫组化法检测心肌组织ATP合成酶亚基(ATP5D)、F-肌动蛋白(F-actin)蛋白表达水平;蛋白免疫印迹法(Western blot)检测心肌组织闭合蛋白(Occludin)、密封蛋白(Claudin)、血管内皮钙黏蛋白(VE-Cadherin)、闭锁小带蛋白1(ZO-1)蛋白表达水平;免疫荧光染色测定微血管密度。结果:与假手术组比较,模型组大鼠射血分数(EF)、左心室缩短分数(FS)显著降低(P<0.01),左室舒张内径(LVIDd)、左室收缩内径(LVIDs)、左室舒张末期后壁厚度(LVPWd)、左室收缩末期后壁厚度(LVPWs)、左室舒张末期容积(LVVOLd)、左室收缩末期容积(LVVOLs)显著升高(P<0.01),NO、VEGF水平显著降低(P<0.01),ET-1、vWF水平显著升高(P<0.01),电镜下微血管基底膜不完整,紧密连接模糊,ATP5D、F-actin蛋白及Occludin、Claudin、ZO-1、VE-Cadherin蛋白表达水平明显降低(P<0.05,P<0.01),微血管相对密度显著降低(P<0.01)。经升陷汤干预后,CHF大鼠EF、FS显著升高(P<0.01),LVIDd、LVIDs、LVPWd、LVPWs、LVVOLd、LVVOLs显著下降(P<0.01),NO、VEGF水平显著升高(P<0.01),ET-1、vWF水平显著下降(P<0.01),电镜下微血管基底膜相对完整,紧密连接相对连续,ATP5D、F-actin及Occludin、Claudin、ZO-1、VE-Cadherin表达水平�Objective:To explore the protective effect of Shengxiantang on cardiac function and myocardial microvascular injury in rats with chronic heart failure(CHF).Methods:The CHF rat model was prepared by aortic arch constriction(TAC).Of the 72 SD rats,8 were randomly selected as the sham operation group,where the chest was opened without ligating the aortic arch.The 40 successfully modeled rats were randomly divided into the model group,the Shengxiantang low-,medium-,and high-dose groups(5.1,10.2,20.4 g·kg^(-1)),and the trimetazidine group(6.3 mg·kg^(-1)),with 8 rats in each group.Drug administration began 4 weeks after modeling.The administration groups received the corresponding drugs by gavage,while the sham operation and model groups were given the same amount of distilled water for 8 consecutive weeks.Echocardiography was used to assess cardiac function.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of nitric oxide(NO),endothelin(ET-1),vascular endothelial growth factor(VEGF),and von Willebrand factor(vWF).Ultrastructural changes of microvessels were observed by transmission electron microscopy.Immunohistochemistry was used to detect the expression levels of ATP synthase subunit(ATP5D)and F-actin in myocardial tissue.Western blot was used to detect the expression levels of occludin,claudin,vascular endothelial cadherin(VE-Cadherin),and zonula occludens-1(ZO-1).Microvessel density was measured by immunofluorescence staining.Results:Compared with the sham operation group,the ejection fraction(EF)and left ventricular shortening fraction(FS)in the model group were significantly decreased(P<0.01),while the left ventricular diastolic diameter(LVIDd),left ventricular systolic diameter(LVIDs),left ventricular end-diastolic posterior wall thickness(LVPWd),left ventricular end-systolic posterior wall thickness(LVPWs),left ventricular end-diastolic volume(LVVOLd),and left ventricular end-systolic volume(LVVOLs)were significantly increased(P<0.01).The levels of NO and VEGF were significantly decreased

关 键 词：慢性心力衰竭 升陷汤 心功能 心肌微血管 

分 类 号：R259[医药卫生—中西医结合] R242[医药卫生—中医内科学] R289[医药卫生—中医学]