瓜蒌薤白半夏汤促进2型糖尿病合并急性心肌缺血大鼠内皮祖细胞动员的作用及其机制  

The effect of Gualou Xiebai Banxia decoction on the mobilization of endothelial progenitor cells in rats of type 2 diabetes complicated with acute myocardial ischemia and its underlying mechanism

作　　者：郑梦梦[1] 赵启韬 周继栋 傅旎旎 胡超群 荀丽英 ZHENG Mengmeng;ZHAO Qitao;ZHOU Jidong;FU Nini;HU Chaoqun;XUN Liying(School of Pharmaceutical Sciences;School of basic medicine, Shandong University of Traditional Chinese Medicine,Jinan,250355,China)

机构地区：[1]山东中医药大学药学院,山东济南250355 [2]山东中医药大学中医学院,山东济南250355

出　　处：《暨南大学学报（自然科学与医学版）》2018年第5期435-441,448,共8页Journal of Jinan University(Natural Science & Medicine Edition)

基　　金：国家自然科学基金项目(81173164; 81573852)

摘　　要：目的:探讨瓜蒌薤白半夏汤(GXB)对2型糖尿病(T2DM)合并急性心肌缺血(AMI)大鼠内皮祖细胞的动员作用及机制,旨在从祖细胞(EPC)层面阐明中药祛痰散结可能的作用机制.方法:将大鼠随机分为3组:对照组、模型组和GXB组,每组再分为7个亚组.首先通过灌胃高脂乳剂造成大鼠高脂血症模型,然后腹腔注射链脲佐菌素制备大鼠2型糖尿病模型. T2DM造模成功后,各组大鼠连续给药7 d.第7天给药30 min后,实施冠状动脉结扎手术,对照组实施假手术.手术后各组大鼠继续灌服GXB或生理盐水.第1～7亚组的大鼠分别于AMI后的第1～7天处死. AMI后连续7 d内,检测并比较各组大鼠每毫升外周血中循环内皮祖细胞(circulating endothelial progenitor cells,CEPCs)含量、血浆中血管内皮生长因子(vascular endothelial growth factor,VEGF)、一氧化氮合成酶(nitric oxide synthetase,e NOS)和一氧化氮(nitric oxide,NO)含量变化,并绘制AMI后7 d内的动态变化曲线.结果:模型组大鼠CEPCs浓度AMI后前3 d急剧升高,第4天达到峰值,随即显著下降;其VEGF、e NOS、NO血浆含量从第3天起显著升高,第4～6天显著下降(P <0. 05或P <0. 01);而GXB组大鼠AMI后1～7天内,CEPCs数量前4天升高幅度和模型组相似,但达到峰值后仍一直维持在较高水平,下降幅度很小.其血浆中VEGF、e NOS、NO含量一直大幅度上升,从第3天起即显著高于同时期模型组(P <0. 05或P <0. 01).结论:瓜蒌薤白半夏汤可能通过上调VEGF、e NOS、NO的表达或分泌来调节骨髓EPC的动员.因此,促进EPC动员是中药祛痰散结功效在祖细胞层次上的体现.Objective:To investigate the effect and mechanism of Gualou Xiebai Banxia decoction(GXB)on endothelial progenitor cells mobilization in rats of type 2 diabetes complicated with acute myocardial ischemia(T2DM-AMI),and to explain the scientific connotation of dispersing phlegm and resolving stagnation of Chinese herbal medicine from the level of progenitor cells.Methods:Rats were randomly divided into 3 groups:control,model,and GXB group.Each group was subdivided into 7 subgroups.Firstly,hyperlipidemia model was induced by intragastric administration of high-fat emulsion,then type 2 diabetes model was then induced by intraperitoneally injecting streptozotocin.After the model was established successful,rats in each group were continuously dosed for 7 days.Thirty minutes after administration on the 7 th day,coronary artery ligation was performed to developed acute myocardial ischemia(AMI)and the control group was subjected to sham surgery.After surgery,rats in each group were continued to receive GXB or saline.Rats in subgroup 1 to 7 were sacrificed on the 1 st to 7 th day after AMI.Within 7 days after AMI,the levels of circulating endothelial progenitor cells(CEPCs),plasma vascular endothelial growth factor(VEGF),nitric oxide synthetase(eNOS)and nitric oxide(NO)in peripheral blood were measured and compared in each group of rats,and the dynamic curve was plotted.Results:The CEPCs concentration in the model group increased sharply in the first 3 days after AMI,peaked on the 4 th day,and then decreased markedly.The plasma levels of VEGF,eNOS,and NO increased significantly from the 3 rd day and decreased significantly from 4 th to 6 th day(P<0.05 or P<0.01).The changes of CEPCs in GXB group was similar to that in the model group in the first 4 days after AMI,however,it still remained at a high level with a slight decrease after reaching the peak value.The level of VEGF,eNOS,and NO in rats of GXB group kept increasing substantially within the 7 days after AMI,and the level was significantly higher than that of model gro

关 键 词：瓜蒌薤白半夏汤 2型糖尿病 急性心肌缺血 内皮细胞 血管内皮生长因子 

分 类 号：R541.4[医药卫生—心血管疾病]