双参宁心胶囊对冠脉微循环障碍大鼠心肌微血管灌注及内皮的影响  

Effects of Shuangshen Ningxin Capsules on myocardial microvascular perfusion and endothelium in ratswith coronarycicrovascularcysfunction

作　　者：李磊[1] 孟红旭[1] 辛高杰 任建勋[1] 郭浩[1] 史跃[1] 马彦雷[1] 刘建勋[1] LI Lei;MENG Hong-xu;XIN Gao-jie;REN Jian-xun;GUO Hao;SHI Yue;MA Yan-lei;LIU Jian-xun(Institute of Basic Medical Sciences of Xiyuan Hospital,China Academy of Chinese Medical Sciences,National Clinical Research Center for Chinese Medicine Cardiology,Beijing Key Laboratory of Chinese Materia Pharmacology,Beijing 100091,China)

机构地区：[1]中国中医科学院西苑医院基础医学研究所,国家中医心血管病临床医学研究中心,中药药理北京市重点实验室,北京100091

出　　处：《中华中医药杂志》2022年第12期7012-7018,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金重点项目(No.82030124);国家自然科学基金面上项目(No.82174015);“重大新药创制”科技重大专项(No.2017ZX09301018);中国中医科学院科技创新工程(No.CI2021A04609)。

摘　　要：目的:研究益气活血中药双参宁心胶囊对冠脉微循环障碍大鼠微血管灌注、内皮功能与形态的影响。方法:60只雄性SD大鼠随机分为6组:假手术组,模型组,尼可地尔组(5mg/kg),双参宁心胶囊高、中、低剂量(180、90、45mg/kg)组,每组10只。按分组先给予相应药物7d,末次给药后2h进行模型制备。采用左心室内注射栓塞微球方法建立大鼠冠脉微循环障碍模型。造模术后24h后,ELISA法检测血清内皮素-1(ET-1)、一氧化氮(NO)及血管紧张素Ⅱ(AngⅡ)水平;采用小动物高分辨率超声影像系统对大鼠进行心肌声学造影,软件系统分析得到微血管密度(A)、局部血流速度(β)、局部心肌灌注量(A·β);利用荧光微球法测定心肌的局部血流量;采用铁矾苏木精伊红(Heidenhain)染色,镜检观察心肌形态变化;以透射电镜观察心肌微血管形态结构。结果:与假手术组比较,模型组血清ET-1、AngⅡ水平显著增高(P<0.01),NO水平显著降低(P<0.01);心肌血液灌注明显降低,A值、β值、A·β值及心肌局部血流量降低(P<0.05,P<0.01);Heidenhain染色大量明显多灶性、弥漫性黑染受损心肌细胞;电镜显示冠脉微血管内皮细胞核严重肿胀,线粒体肿胀,微饮泡减少。与模型组比较,双参宁心胶囊能显著升高NO(P<0.01)、降低ET-1、AngⅡ水平(P<0.01);改善心肌血液灌注,显著增加A值、β值及A·β值(P<0.05,P<0.01);显著增加心肌的局部血流量(P<0.05);改善Heidenhain染色所示的急性心肌缺血;改善大鼠心肌微血管内皮超微结构损伤,增加胞浆微饮泡。结论:双参宁心胶囊能改善冠脉微循环障碍大鼠心肌组织损伤,其机制可能与增加冠脉微血管开放,改善心肌血流灌注及内皮功能异常有关。Objective: To study the effects of Shuangshen Ningxin Capsules(SSNX) on microvascular perfusion,endothelial function and morphology in rats with coronary microvascular dysfunction. Methods: Sixty male SD rats were randomly divided into 6 groups: sham operation group, model group, nicorandil group(5 mg/kg), SSNX high, medium and low doses(180,90, 45 mg/kg) group, 10 rats in each group. Animals were given the corresponding drugs for 7 days, and the model was prepared 2 hours after the last dose. The left ventricular injection of embolic microspheres was used to establish a rat model coronary microvascular dysfunction. The serum levels of endothelin-1(ET-1), nitric oxide(NO) and angiotensin Ⅱ(AngⅡ) were detected by ELISA at 24 h after modeling. A small animal high-resolution ultrasound imaging system was used to perform myocardial contrast echocardiography in rats. The microvessel density(A), local blood velocity(β) and regional myocardial perfusion(A·β) were obtained by software system analysis. Fluorescent microsphere technique were used to observe the myocardial local blood flow.Heidenhain stain to observe the morphological changes of myocardium. Transmission electron microscope was used to detect changes in myocardial microvascular structure. Results: Compared with the sham operation group, serum ET-1 and AngⅡ in the model group was significantly increased(P<0.01), and NO was significantly decreased(P<0.01). Myocardial blood perfusion was significantly reduced, A value, β value, A·β value and myocardial local blood flow was reduced(P<0.05, P<0.01). Heidenhain staining showed a large number of obviously multifocal and diffuse black stained damaged cardiomyocytes. Electron microscope showed severe swelling of coronary microvascular endothelial cell nuclei, swelling of mitochondria, and reduction of pinocytoic vesicles. Compared with the model group, SSNX can significantly increase NO and decrease ET-1 and Ang Ⅱ levels(P<0.01).Myocardial blood perfusion was significantly improved, A value, β value an

关 键 词：双参宁心胶囊 益气活血中药 冠脉微循环障碍 微血管灌注 心肌局部血流 

分 类 号：R285.5[医药卫生—中药学]