五参汤加减对心肌梗死大鼠心脏功能及促血管生成作用的保护机制研究  

Study on Protective Mechanism of Modified Wushen Decoction(五参汤)on Cardiac Function and Angiogenesis Promotion in Rats with Myocardial Infarction

作　　者：张富璋 鲁卫星 ZHANG Fuzhang;LU Weixing(Beijing University of Chinese Medicine,Beijing 100029,China;Third Affiliated Hospital of Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学,北京100029 [2]北京中医药大学第三附属医院,北京100029

出　　处：《中医药导报》2023年第10期18-22,共5页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：北京自然科学基金项目(7172124)。

摘　　要：目的:探究五参汤加减对心肌梗死大鼠心脏功能和血管生成的影响及机制。方法:从82只SD大鼠中随机选出10只作为假手术组,其余大鼠建立心肌梗死模型,造模成功后将大鼠随机分为模型组、阳性对照组、五参汤加减低剂量组、五参汤加减中剂量组、五参汤加减高剂量组,每组10只。各药物组大鼠灌胃给予相应药物,假手术组和模型组大鼠予等体积生理盐水灌胃,1次/d,连续给药14 d。采用超声心动图评价心脏功能,HE染色观察心肌组织病理学变化,免疫组化染色血小板-内皮细胞黏附分子(CD31)检测微血管密度(MVD),ELISA法检测大鼠血清肌酸激酶MB(CK-MB)、脑钠肽(BNP)、肿瘤坏死因子-α(TNF-α)水平,qRT-PCR和Western blotting法检测心肌组织促血管生成相关基因和蛋白表达。结果:与假手术组比较,模型组大鼠心肌组织存在明显病理改变,LVEDD、LVESD、MVD、CK-MB、BNP、TNF-α均明显升高(P<0.05),LVFS、LVEF均明显降低(P<0.05);与模型组比较,阳性对照组和五参汤加减中、高剂量组大鼠心肌病理改变明显改善,LVEDD、LVESD、MVD、CK-MB、BNP、TNF-α均明显降低(P<0.05),LVFS、LVEF均明显升高(P<0.05)。与假手术组比较,模型组大鼠心肌组织VEGF、PI3K的mRNA与蛋白相对表达量、AKT mRNA相对表达量和p-AKT/AKT均明显降低(P<0.05);与模型组比较,阳性对照组和五参汤加减中、高剂量组大鼠心肌组织VEGF、PI3K的mRNA与蛋白相对表达量、AKT mRNA相对表达量和p-AKT/AKT均明显升高(P<0.05);五参汤加减低剂量组大鼠心肌组织VEGF、PI3K的mRNA与蛋白相对表达量、AKT mRNA相对表达量和p-AKT/AKT与模型组比较,差异无统计学意义(P>0.05)。结论:五参汤加减可改善心肌梗死大鼠心脏功能和心脏重塑,减轻炎症反应,促血管生成,其机制可能与调控PI3K/AKT信号通路相关。Objective:To explore the roles and mechanism of modified Wushen decoction on cardiac function and angiogenesis in rats with myocardial infarction.Methods:Totally 10 rats were randomly selected from 82 SD rats as the sham operation group,and the remaining rats were established myocardial infarction model.The myocardial infarction model was established by ligation of coronary artery.The successful modeling rats were randomly divided into model group,positive control group(benazepril),low-dose modified Wushen decoction group,middle-dose modified Wushen decoction group and high-dose modified Wushen decoction group,with 10 rats in each group.After 14 days of treatment,echocardiogram was applied to evaluate the cardiac function.HE staining was used to observe myocardial histopathological changes,and immunohistochemical staining for platelet-endothelial cell adhesion molecule(CD31)was used to detect microvessel density(MVD).ELISA was used to detect levels of serum creatine kinase MB(CK-MB),brain natriuretic peptide(BNP)and tumor necrosis factor-α(TNF-α).qRT-PCR and Western blotting were used for the expressions of angiogenesis-related genes and proteins in myocardial tissues.Results:Compared with the sham operation group,the model group showed obvious pathological changes in the myocardium,with increased LVEDD,LVESD,MVD,CK-MB,BNP and TNF-α(P<0.05)and decreased LVFS and LVEF(P<0.05).Compared with model group,the myocardial pathological changes were improved in the positive control group,middle-dose modified Wushen decoction group and high-dose modified Wushen decoction group,and the LVEDD,LVESD,MVD,CK-MB,BNP and TNF-αwere reduced(P<0.05),while the LVFS and LVEF were enhanced(P<0.05).Compared with sham operation group,mRNA and protein relative expression levels of VEGF and PI3K,mRNA relative expression levels of AKT and P-AKT/AKT in myocardium were significantly decreased in model group(P<0.05).Compared with model group,the mRNA and protein relative expression levels of VEGF and PI3K,mRNA relative expression level of

关 键 词：心肌梗死 五参汤加减 血管生成 PI3K/AKT信号通路 大鼠 

分 类 号：R285.5[医药卫生—中药学]