促红细胞生成素对慢性心力衰竭小鼠急性失代偿的保护机制  

Mechanisms underlying protective effect of erythropoietin on acute decompensated congestive heart failure in mice

作　　者：李力[1] 杨国栋[1] 段伟[1] 张红超[2] 

机构地区：[1]河北北方学院,张家口075000 [2]北京空军总医院心外科,北京100142

出　　处：《中国新药杂志》2011年第7期619-624,共6页Chinese Journal of New Drugs

基　　金：国家自然科学基金(30872539)

摘　　要：目的:探讨促红细胞生成素(erythropoietin,EPO)对脂多糖(lipopolysaccharides,LPS)诱导的急性失代偿性心力衰竭(acute decompensated heart hailure,ADHF)的保护机制。方法:50只C57Bl/6小鼠随机分为空白(Nor)组、阿霉素(doxorubicin,Dox)组、阿霉素感染(Dox+LPS,D&L)组、阿霉素治疗(Dox+EPO,D&E)组和阿霉素感染治疗组(Dox+LPS+EPO,DLE),每组10只。前5周,除Nor组外,其他组腹腔注射Dox(每次5 mg.kg-1,1次.周-1,共5周),建立CHF小鼠模型。第7周时,D&L和DLE组腹腔注射单剂LPS 5 mg.kg-1,D&E和DLE组腹腔注射单剂EPO5 000 iu.kg-1。观察1周后,第8周行心脏超声检查、血清中白介素-6(interleukin-6,IL-6)和脑钠肽(brain natriuretic peptide,BNP)含量测定、HWI、心肌组织的免疫组织化学分析P-STAT3,Bcl-2和Bax蛋白的表达。结果:与D&L组相比,DLE组小鼠给予EPO处理后心室壁厚度、射血分数(ejection fraction,EF)也明显增高(P<0.01);P-STAT3和Bcl-2表达增加,Bax表达减少(P<0.05);但IL-6蛋白表达改变不明显。结论:EPO的抗炎作用对LPS诱导的炎症反应影响不明显,但可增强心肌细胞本身对炎症损伤防御机制。Objective： To determine the mechanisms underlying protective effect of erythropoietin（EPO） on acute decompensated heart failure（ADHF） induced by lipopolysaccharides（LPS） in mice.Methods： We randomly divided mice into 5 groups（n=10 in each group）.In the first 5 weeks,congestive heart failure（CHF） was induced by ip doxorubicin 5 mg·kg^-1once a week for 5 weeks.In the seventh week,LPS 5 mg·kg^-1was ip injected.Meanwhile,EPO 5 000 iu·kg-1 was ip injected,and mice were observed for one week.In the eighth week,the heart was examined with ultrasound,contents of IL-6,BNP and HWI were detected,and the expressions of P-STAT3,Bcl-2 and Bax in cardiac tissues were analyzed by immunohistochemistry.Results： Compared with CHF control,EPO significantly heightened the thickness of ventricular wall and increased ejection fraction（EF） peak（P〈0.01）;reduced the expression of Bcl-2,Bax and P-STAT3（P〈0.05）,respectively;but did not affect IL-6 expression.Conclusion： EPO has little effect on the inflammation induced by LPS,but it enhances the protective mechanisms against inflammatory injuries in cardiac tissues in ADHF mice.

关 键 词：促红细胞生成素 心力衰竭 急性失代偿 内毒素 阿霉素 白细胞介素-6 脑钠肽 

分 类 号：R972[医药卫生—药品]