双参宁心胶囊对2型糖尿病大鼠冠状动脉微循环的影响  

Effect of Shuangshen Ningxin Capsules on Coronary Microcirculation in Type 2 Diabetes Mellitus Rats

作　　者：王攀 韩笑[1] 任建勋[1] 彭菊琴 陈潇潇 刘哲 刘建勋[1] 任钧国[1] WANG Pan;HAN Xiao;REN Jianxun;PENG Juqin;CHEN Xiaoxiao;LIU Zhe;LIU Jianxun;REN Junguo(Institute of Basic Medical Sciences of Xiyuan Hospital,China Academy of Chinese Medical Sciences,National Clinical Research Center for Cardiovascular Diseases of Traditional Chinese Medicine,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：《中国中医药信息杂志》2022年第6期69-74,共6页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家科技重大专项-重大新药创制(2017ZX09301018)。

摘　　要：目的观察双参宁心胶囊对2型糖尿病大鼠冠状动脉微循环的影响,探讨其作用机制。方法健康Wistar大鼠随机分为正常组和造模组,造模组采用高糖高脂饲料喂养联合腹腔注射链脲佐菌素(30 mg/kg)建立2型糖尿病大鼠模型。将成模大鼠随机分为模型组、尼可地尔组(5 mg/kg)和双参宁心胶囊高(180 mg/kg)、低(90 mg/kg)剂量组,给药组分别给予相应药物灌胃,正常组和模型组予等体积蒸馏水灌胃,每日1次,连续4周。采用超高分辨率小动物超声仪检测大鼠心肌灌注情况,ELISA检测血清血管细胞黏附分子-1(VCAM-1)、血管内皮钙黏蛋白(VE-cadherin)含量,透射电镜观察心肌微血管形态,免疫组化染色检测心肌微血管密度(MVD),Western blot检测心肌组织血管内皮生长因子A(VEGFA)蛋白表达。结果与正常组比较,模型组大鼠心肌微血管基底膜增厚,部分断裂或消失,心肌灌注能力明显降低(P<0.01);血清VCAM-1含量明显增加,VE-cadherin含量明显减少(P<0.01),心肌MVD明显降低(P<0.01),心肌组织VEGFA蛋白表达明显降低(P<0.05)。与模型组比较,双参宁心胶囊高、低剂量组大鼠心肌微血管结构较完整,微血管细胞间紧密连接,心肌灌注能力明显升高(P<0.01);双参宁心胶囊低剂量组大鼠血清VCAM-1含量明显减少(P<0.01),VE-cadherin含量明显增加(P<0.01),双参宁心胶囊高、低剂量组大鼠心肌MVD明显升高(P<0.05),心肌组织VEGFA蛋白表达明显升高(P<0.01,P<0.05)。结论双参宁心胶囊可能通过调节血管内皮活性物质,保护心肌微血管结构,促进心肌微血管生成,从而改善2型糖尿病大鼠冠状动脉微循环。Objective To observe the effects of Shuangshen Ningxin Capsules on coronary microcirculation in type 2 diabetes mellitus rats;To discuss its mechanism.Methods Healthy Wistar rats were randomly divided into normal group and modeling group.The modeling group was fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(30 mg/kg)to establish a rat model of type 2 diabetes mellitus.The model rats were randomly divided into model group,nicorandil group(5 mg/kg)and Shuangshen Ningxin Capsules high(180 mg/kg)-and low(90 mg/kg)-dosage groups.The administered groups were given corresponding drugs by gavage respectively,and the normal group and the model group were given an equal volume of distilled water by gavage,once a day,for 4 consecutive weeks.Myocardial perfusion in rats were detected by ultra-high-resolution small animal ultrasound;ELISA was used to detect the contents of VCAM-1 and VE-cadherin in serum;transmission electron microscopy was used to observe the morphology of myocardial microvessels;immunohistochemical staining was used to detect myocardial microvessel density;Western blot was used to detect the expression of myocardial VEGFA protein.Results Compared with the normal group,the basement membrane of myocardial microvessels of rats in model group was thickened,partially broken and disappeared,the myocardial perfusion ability was decreased(P<0.01),the content of VCAM-1 in serum significantly increased,the content of VE-cadherin significantly reduced(P<0.01),the myocardial microvessel density was decreased significantly(P<0.01),the expression of myocardial VEGFA protein significantly decreased(P<0.05).Compared with the model group,the structure of myocardial microvascular in Shuangshen Ningxin Capsules high-and low-dosage group were relatively complete,the microvascular cells were tightly connected,the myocardial perfusion ability was significantly increased(P<0.01);the content of VCAM-1 in serum of the rats in Shuangshen Ningxin Capsules low-dosage group significantly

关 键 词：双参宁心胶囊 2型糖尿病 冠状动脉微循环 血管内皮生长因子A 大鼠 

分 类 号：R285.5[医药卫生—中药学]