血府逐瘀汤对心肌缺血大鼠外周血内皮祖细胞衰老的作用机制研究  

Effect and mechanism of Xuefu Zhuyu Decoction on the senescence of peripheral blood endothelial progenitor cells in myocardial ischemia rats

作　　者：杨漾 苏畅 邹蔓姝 梁昊 张秋雁 李蕾 YANG Yang;SU Chang;ZOU Man-shu;LIANG Hao;ZHANG Qiu-yan;LI Lei(College of Chinese Medicine,Hunan University of Traditional Chinese Medicine,Changsha 410208,Hunan Province,China;Xiangxing College,Hunan University of Traditional Chinese Medicine,Changsha 410208,Hunan Province,China;Technology Innovation Center,Hunan University of Traditional Chinese Medicine,Changsha 410208,Hunan Province,China;School Infirmary,Hunan University of Traditional Chinese Medicine,Changsha 410208,Hunan Province,China)

机构地区：[1]湖南中医药大学中医学院,湖南长沙410208 [2]湖南中医药大学湘杏学院,湖南长沙410208 [3]湖南中医药大学科技创新中心,湖南长沙410208 [4]湖南中医药大学校医院,湖南长沙410208

出　　处：《中国临床药理学杂志》2021年第14期1832-1835,1839,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81574039);湖南省自然科学基金资助项目(2020JJ4471)。

摘　　要：目的观察血府逐瘀汤对心肌缺血大鼠外周血内皮祖细胞(EPCs)衰老及抑癌基因p53、沉默信息调节因子(SIRT1)蛋白表达的影响。方法结扎冠状动脉左前降支建立心肌缺血大鼠模型。按照体重将大鼠随机分为7组:正常组、假手术组、模型组、他汀组和低、中、高3个剂量实验组,每组8只。造模成功后第2天开始给药。他汀组腹腔注射阿托伐他汀0.3 mg,低、中、高剂量组灌胃药液3.51,7.02,14.04 g·kg^(-1),1次/天。于灌胃前和灌胃第3天、第7天,经眼眶内眦静脉丛采血并分离外周血EPCs。以β-半乳糖苷酶染色法检测EPCs衰老状态;以蛋白质印迹法检测EPCs中p53、SIRT1蛋白的表达。结果灌胃第7天,正常组、假手术组、模型组、他汀组和低、中、高3个剂量实验组的EPCs衰老率分别为(58.38±5.24)%,(53.00±3.16)%,(73.63±3.02)%,(64.25±2.66)%,(67.38±5.07)%,(65.25±3.92)%和(59.50±4.24)%;这7组p53蛋白表达量分别为0.26±0.01,0.34±0.02,0.48±0.03,0.10±0.01,0.26±0.02,0.20±0.02和0.12±0.01;这7组SIRT1蛋白表达量分别为0.55±0.02,0.35±0.02,0.14±0.03,0.49±0.08,0.21±0.05,0.39±0.10和0.45±0.08。上述这3个指标,模型组与正常组比较,差异均有统计学意义(P<0.01);3个剂量实验组与模型组比较,差异均有统计学意义(P<0.05)。结论血府逐瘀汤能延缓心肌缺血大鼠外周血EPCs的衰老,降低心肌缺血大鼠外周血EPCs中p53蛋白的表达而增加SIRT1蛋白的表达,其中以高剂量实验组和灌胃第7天效果最佳。Objective To observe the effects of Xuefu Zhuyu Decoction on the senescence of endothelial progenitor cells(EPCs)and the expression of tumor suppressor p53 and silencing information regulator 1(SIRT1)in peripheral blood of rats with myocardial ischemia.Methods The left anterior descending coronary artery was ligated to establish a rat model of myocardial ischemia.The rats were randomly divided into 7 groups according to weight:normal group(no treatment),sham operation group(only threading and no ligation),model group(orally administer with normal saline),atorvastatin group(intraperitoneal injection with atorvastatin at the dose of 0.3 mg)and low,medium and high dose experimental groups(orally administer with Xuefu Zhuyu Decoction at the dose of 3.51,7.02,14.04 g·kg^(-1),respectively),8 rats in each group;1 times per day for 3 d or 7 d.Before gavage and on the 3rd day and 7th day after gavage,blood was collected to separate the peripheral blood EPCs.The senescence rate of EPCs was detected byβ-galactosidase staining method.The protein expression of P53 and SIRT1 was detected by Western blot.Results On the 7th day after gavage,the senescence rate of EPCs in the normal group,sham operation group,model group,atorvastatin group and low,medium and high dose experimental groups were(58.38±5.24)%,(53.00±3.16)%,(73.63±3.02)%,(64.25±2.66)%,(67.38±5.07)%,(65.25±3.92)%,(59.50±4.24)%,respectively;the protein expression levels of p53 in these 7 groups were 0.26±0.01,0.34±0.02,0.48±0.03,0.10±0.01,0.26±0.02,0.20±0.02 and 0.12±0.01;the protein expression levels of SIRT1 in these 7 groups were 0.55±0.02,0.35±0.02,0.14±0.03,0.49±0.08,0.21±0.05,0.39±0.10 and 0.45±0.08.Significant difference of the factors was found between normal group and model group(all P<0.01),and significant difference of the factors was also found between the three experimental groups and model group(all P<0.05).Conclusion The aging of peripheral blood EPCs in rats with myocardial ischemia were markedly delayed by Xuefu Zhuyu Decoction,th

关 键 词：血府逐瘀汤 心肌缺血 内皮祖细胞 细胞衰老 肿瘤抑制基因P53 沉默信息调节因子1 

分 类 号：R28[医药卫生—中药学]