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心肌内注射17β-雌二醇纳米粒的促血管生成效应及相关机制研究(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2008年第1期
页码:
17-20
栏目:
基础研究
出版日期:
2008-01-20

文章信息/Info

Title:
Effect of intramyocardial administration of 17βestradiol loaded nanoparticles on angiogenesis in rats after myocardial infarction
作者:
刘伟强1;  陈玉成1;  熊素彬2;  曾智1
1.四川大学华西医院心内科,四川 成都 610041; 2.浙江工业大学药学院，浙江 杭州 310032
Author(s):
LIU Weiqiang1;  CHEN Yucheng1;  XIONG Subin2;  ZENG Zhi1
1.Department of Cardiology, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; 2.College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, Zhejiang, China
关键词:
心肌梗死;  雌二醇;  血管生成
Keywords:
myocardial infarction;  estradiol;  angiogenesis
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的 评价心肌内局部注射聚乳酸和乙醇酸共聚物(polydllacticCOglycolic acid,PLGA)纳米粒包载17β-雌二醇促大鼠心肌梗死（心梗）后心肌血管生成效应及其作用与内源性雌激素关系。方法 乳化/液体蒸发法制备17β-雌二醇纳米粒, 检测其理化性质和体外药物释放参数。制备大鼠心梗模型, 随机分为去卵巢心梗治疗（ET）组、去卵巢心梗对照（OMI）组、正常卵巢心梗对照（MI）组。1月后免疫组化法检测心梗边缘区毛细血管密度(microvascular density,MVD) 及eNOS蛋白表达, 放免法检测血清17β-雌二醇浓度。结果 体外释放参数显示, 17β-雌二醇从PLGA纳米粒载体中持续释放1月。心梗1月后免疫组化法显示ET组MVD、eNOS蛋白表达比MI组显著增加(P<0.05); 与MI组比较, OMI组MVD、eNOS蛋白表达均减少(P<0.05)。结论 内源性雌激素缺乏负面影响心肌毛细血管生成。心肌内局部注射17β-雌二醇纳米粒不依赖内源性雌激素发挥促大鼠心梗后心肌毛细血管生成作用, 机制可能与其增加心肌eNOS蛋白表达有关。
Abstract:
AIM To experimentally investigate the effect of direct intramyocardial administration of 17β-estradiol loaded nanoparticles on myocardial angiogenesis in rats after myocardial infarction. METHODS 17β-estradiol loaded nanoparticles were prepared by a solvent evaporation method. Release parameters were detected in vitro experiment. Myocardial infarction was induced by left coronary artery ligation in ovariectomized female rats treated with intramyocardial administration of 17β-estradiol loaded nanoparticles (4 mg/100 g). One month later, the microvascular density (MVD) and eNOS protein expression in myocardium of the rats were analyzed by immunohistochemistry and the serum levels of 17βestradiol were measured by RIA method. RESULTSIn vitro 17βestradiol release was maintained at a constant rate from these PLGA nanoparticles for 1 month. One month after operation, the MVD and eNOS protein expressions were higher in myocardium of rats in ET group than those in MI group (P<0.05). A significant decrease in MVD and eNOS protein expression was observed in OMI grou, compared with that in MI group. CONCLUSIONS 17β-estrogen deficiency induced by oophorectomy negatively affects myocardial angiogenesis. Local intramyocardial administration of 17βestradiol loaded nanoparticles can effectively promote angiogenesis of myocardium in rats, which may attribute to the increased eNOS protein.

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备注/Memo

备注/Memo:
收稿日期：2007-09-03.基金项目: 教育部博士点基金项目资助（20040610057）通讯作者:曾智,主任医师, 主要从事冠心病基础与临床研究Email: chenyucheng2003@126.com作者简介:刘伟强, 主治医师, 硕士生Email:hxydlwq@sohu.com
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