心肌内注射17β-雌二醇纳米粒对大鼠心肌梗死影响的研究  

The effects of intramyocardial injection of 17β-estradiol-loaded nanoparticles on myocardial infarction in rats

作　　者：刘伟强[1] 陈玉成[1] 熊素彬[2] 曾智[1] 金鑫[1] 王斌[1] 王浩宇[1] 

机构地区：[1]四川大学华西医院心内科,成都610041 [2]浙江工业大学药学院

出　　处：《中华老年心脑血管病杂志》2008年第9期691-694,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：教育部博士点基金(20040610057)

摘　　要：目的探讨心肌内局部注射17β-雌二醇纳米粒对大鼠心肌梗死后血管生成、梗死面积、死亡率的影响。方法以聚乳酸和乙醇酸共聚物(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、体外药物释放参数。将75只SD雌鼠制备去卵巢心肌梗死模型,制模成功60只大鼠随机分为实验组(梗死边缘区注射17β-雌二醇纳米粒4mg/100g)、实验对照组(梗死边缘区注射空白纳米粒4mg/100g)和空白对照组(仅制备去卵巢心肌梗死模型),每组20只。1个月后免疫组织化学法检测心肌梗死边缘区毛细血管密度(MVD)及内皮型一氧化氮合酶(eNOS)累积吸光度(A)值,并测量梗死面积。结果17β-雌二醇从PLGA纳米粒载体中缓慢释放1个月,与空白对照组和实验对照组比较,实验组心肌梗死1个月后梗死边缘区MVD增加(P<0.05),eNOSA值增多(P<0.05),梗死面积减小(P<0.05),死亡率无升高(P=1.000)。结论心肌内局部注射17β-雌二醇纳米粒可以促使大鼠心肌梗死后心肌毛细血管生成,减少心肌梗死面积,不增加死亡率。Objective To experimentally investigate the effects of intramyocardial injection of 17β-estradiol-loaded nanoparticles on angiogenesis,infarct size and mortality in SD rats after myocardial infarction（MI） . Methods 17β-estradiol-loaded nanoparticles were prepared by a solvent evaporation method with PLGA nanoparticles as the carrier. MI was induced by ligation of left coronary artery in ovariectomized SD rats. Then 17β-estradiol-loaded nanoparticles or bare nanoparticles were injected in to infarct area. One month later, microvascular density（MVD） and eNOS protein expression in myocardium of SD rats after MI were detected by immunohistochemistry. Results The 17β-estradiol release was maintained at a constant rate from PLGA nanoparticles for one month. One month after operation, the MVD and eNOS protein expression in 17β-estradiol loaded nanoparticles group increased compared with control group （P〈0.05）. Moreover,a significant reduction in infarct size was observed in 17β-estradiol-loaded nanoparticles group compared with control group （P 〈0.05）. The mortality was not different between experiment group and control groups （P = 1. 000）. Conclusions Local intramyocardial injection of 17β-estradiol-loaded nanoparticles can effectively promote angiogenesis and decrease infarct size after MI,and does not increase mortality. These results suggest that intramyocardial injection of 17β-estradiol-loaded nanoparticles may be a new useful therapy for patients with MI.

关 键 词：雌二醇 心肌梗塞 新生血管化 生理化 纳米技术 迟效制剂 

分 类 号：R96[医药卫生—药理学]