冠心病心血瘀阻证模型大鼠的建立及方药评价  

Establishment of Rat Model of Coronary Heart Disease with Xinxueyuzu(心血瘀阻)Syndrome and Evaluation of Prescription Efficacy

作　　者：李静[1,2] 郭志华[1,2] 刘建和[3] 钟森杰 匡慧芳 梁昊[1] 杨漾 张斐 张秋雁[1] LI Jing;GUO Zhihua;LIU Jianhe;ZHONG Senjie;KUANG Huifang;LIANG Hao;YANG Yang;ZHANG Fei;ZHANG Qiuyan(Hunan University of Chinese Medicine,Changsha 410208;Hunan Key Laboratory of Colleges and Universities of Intelligent Traditional Chinese Medicine Diagnosis and Preventive Treatment of Chronic Diseases,Hunan University of Chinese Medicine,Changsha 410208;The First Hospital of Hunan University of Chinese Medicine,Changsha 410007;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405)

机构地区：[1]湖南中医药大学,长沙410208 [2]湖南中医药大学慢病中医智能诊断与治未病湖南省普通高等学校重点实验室,长沙410208 [3]湖南中医药大学第一附属医院,长沙410007 [4]广州中医药大学第一附属医院,广州510405

出　　处：《中药药理与临床》2024年第1期86-93,共8页Pharmacology and Clinics of Chinese Materia Medica

基　　金：湖南省教育厅重点项目(编号:21A0253);湖南中医药大学2022年度学科建设“揭榜挂帅”项目(编号:22JBZ005);国家自然科学基金(编号:81574039、82174343);中药粉体与创新药物省部共建国家重点实验室培育基地开放基金项目(编号:21PTKF1012);湖南中医药大学2022年研究生创新项目(编号:2022CX04)。

摘　　要：目的:研究冠状动脉左前降支结扎模型的病理特点及血府逐瘀汤的干预效应,以“方证对应”理论探讨冠心病心血瘀阻证模型的建立方法。方法:通过结扎冠状动脉左前降支法制备冠心病模型大鼠,随机分为正常对照组、假手术对照组、模型对照组、血府逐瘀汤14 g/kg组、曲美他嗪5.4 mg/kg组,连续灌胃给药14 d。观察舌象色度测定R(Red,红色)、G(Green,绿色)、B(Blue,蓝色)分量值;心电图检测心率及ST段的变化;超声心动图检测心功能指标,包括左室射血分数(LVEF)、短轴缩短率(LVFS)、左室收缩末内径(LVIDs)、左室舒张末内径(LVIDd);血液流变学检测全血黏度、卡松粘度和红细胞聚集指数;HE染色观察心肌组织病理学变化;Masson染色观察心肌组织纤维化情况,使用Image J软件计算胶原容积分数(CVF)、透射电镜观察心肌细胞超微结构变化;ELISA法检测血清血栓素B2(TXB2)、6-酮-前列腺素1α(6-keto-PGF1α)、纤溶酶原激活物抑制剂-1(PAI-1)、组织型纤溶酶原激活物(t-PA)含量;免疫组化(IHC)法检测心肌组织细胞间粘附分子-1(ICAM-1)、血管内皮细胞粘附分子-1(VCAM-1)蛋白阳性表达情况。结果:与正常对照组、假手术对照组比较,模型对照组大鼠舌象R、G、B值均显著降低(P<0.01);心电图心率、ST段抬高幅度显著升高(P<0.01);LVEF、LVFS值显著下降,LVIDd、LVIDs值显著升高(P<0.01);心肌组织病理形态学显示心肌细胞排列紊乱、有大量炎性细胞浸润、胶原纤维增多、CVF显著升高(P<0.01),线粒体膜、嵴结构出现肿胀、断裂、溶解,可见空泡化改变;全血粘度(低、中、高切)、卡松粘度、红细胞聚集指数显著升高(P<0.01);TXB2、PAI-1含量显著升高(P<0.01),6-keto-PGF1α、t-PA含量显著降低(P<0.01);黏附因子ICAM-1、VCAM-1蛋白阳性表达显著升高(P<0.01)。与模型对照组比较,血府逐瘀汤14 g/kg组可显著升高大鼠舌象R、G、B值,心电图心率、ST段�Objective:To investigate the pathological features of the model established by left anterior descending coronary artery ligation and the intervention effect of Xuefuzhuyu(血府逐瘀)Decoction,and explore the establishment method of Xinxueyuzu(心血瘀阻)Syndrome based on the theory of prescription corresponding to syndrome.Methods:A rat model of coronary heart disease was established by left anterior descending coronary artery ligation.Rats were randomized into normal control,sham surgery,model control,Xuefuzhuyu Decoction(14 g/kg),and trimetazidine(5.4 mg/kg)groups.All the rats were administered with corresponding drugs by gavage for 14 days.A tongue color analyzer was used to determine the R(red),G(green),and B(blue)values of the tongue.The heart rate and ST segment changes were observed by electrocardiogram(ECG)measurement.Echocardiography was employed to determine the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-systolic diameter(LVIDs),and left ventricular end-diastolic diameter(LVIDd).The whole blood viscosity,Casson viscosity,and red blood cell aggregation index were determined.Hematoxylin-eosin(HE)staining and Masson’s staining were performed to observe histopathological changes and myocardial fibrosis,respectively.Image J was used to calculate the collagen volume fraction(CVF).Transmission electron microscopy was employed to observe the ultrastructural changes in myocardial cells.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the serum levels of thromboxane B2(TXB2),6-ketoprostaglandin F1α(6-keto-PGF1α),plasminogen activator inhibitor-1(PAI-1),and tissue-type plasminogen activator(t-PA).Immunohistochemistry(IHC)was employed to assess the positive expression of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)in the myocardial tissue.Results:Compared with the normal control group and the sham surgery group,the model control group showed decreases in tongue R,G,and B values(P<0.01),in

关 键 词：冠心病 心血瘀阻证 病证结合 血府逐瘀汤 

分 类 号：R285.5[医药卫生—中药学]