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心肌内注射17β-雌二醇纳米粒对大鼠心梗的修复作用

o Repair Myocardial Infarction in rats through Intramyocardial Administration of 17β-Estradiol Loaded Nanoparticle

中文摘要英文摘要

目的 探讨心肌内局部肌注17β-雌二醇纳米粒对大鼠心梗后血管生成、梗死面积、死亡率的影响。方法 以聚乳酸和乙醇酸共聚物(poly-dl-lactic-CO-glycolic acid,PLGA)纳米粒为载体制备17β-雌二醇纳米粒,评价其理化性质及体内、外药物释放参数.制备去卵巢大鼠心梗模型,随机分为实验组(在心梗边缘区注射17β-雌二醇纳米粒4mg/100g,n=20),实验对照组(在心梗边缘区注射空白纳米粒4mg/100g,n=20 ),空白对照组(仅制备去卵巢心梗模型,n=20).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累积光密度(IOD)值,测量梗死面积。结果 体外释放参数显示,1月时17β-雌二醇累积释放率已接近100%,体内释放曲线显示心肌内注射1月后血清仍保持较高药物浓度(345.480 ±8.906pg/ml).心梗1月后与对照组相比,实验组免疫组化法显示梗死边缘区毛细血管密度增加(P<0.05),eNOS蛋白IOD值增多(P<0.05),梗死面积减小(P<0.05),死亡率无升高(P>0.05)。结论 心肌内局部注射17β-雌二醇纳米粒可有效促进大鼠梗死后心肌毛细血管生成,减少心梗面积,不增加死亡率,对心梗有较好的修复作用.

objective To experimentally investigate the efficiency of direct intramyocardial administration of 17β-estradiol loaded nanoparticles on angiogenesis, infarct size and mortality after myocardial infarction (MI) in rats. Methods PLGA (poly-dl-lactic-CO-glycolic acid) nanoparticles containing 0.24% (w/w) of estradiol were prepared by a solvent evaporation method. And then release parameters were detected in vivo and vitro experiments. Myocardial infarction was induced by ligation of Ieft coronary artery in ovariectomized rats receiving either 17β-estradiol loaded nanoparticles or bare nanoparticle.one month later, microvascular density(MVD) and eNOS protein expression in myocardium of rats after MI were detected by immunohistochemistry, and infarct size in the infarct region was measured with previous experimental method. Results The 17β-estradiol release was maintained at a constant rate form PLGA nanoparticles for one month.one month later,The MVD and eNOS protein were higher in myocardium of rats after MI in 17β-estradiol loaded nanoparticles group than that in control group(P<0.05).moreover, a significant reduction in infarct size was observed in 17β-estradiol loaded nanoparticles group,compared with MI rats receiving bare nanoparticle(P<0.05). The mortality was not different in all groups(P>0.05). conclusions local intramyocardial administration of 17β-estradiol loaded nanoparticles can effectively promote angiogenesis and decrease infarct size after MI in rats,and do not increase mortality.

熊素彬、刘伟强、陈玉成、王浩宇、曾智、金鑫、王斌

基础医学内科学药学

雌二醇纳米粒血管生成梗死面积

estradiolnanoparticlesangiogenesisinfarct size

熊素彬,刘伟强,陈玉成,王浩宇,曾智,金鑫,王斌.心肌内注射17β-雌二醇纳米粒对大鼠心梗的修复作用[EB/OL].(2007-09-13)[2025-08-11].http://www.paper.edu.cn/releasepaper/content/200709-244.点此复制

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