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促红细胞生成素抑制心梗大鼠心肌核转录因子CHOP表达的研究
Inhibition of Erythropoietin Protection on CHOP Expression of Myocardial Infarction Rats
【摘要】 目的探讨促红细胞生成素(erythropoietin,EPO)抑制心梗大鼠心肌核转录因子CHOP(C/EBP homologous protein)表达的作用。方法将雄性SD大鼠30只随机分为假手术对照组、心肌梗死组和EPO治疗组。心肌梗死组及心肌梗死EPO治疗组采用结扎左冠状动脉前降支建立心梗模型。其中EPO治疗组术后每天腹腔注射重组人促红细胞生成素(recombinant human erythropoietin,rh-EPO)(1 000 u.kg-1),其余2组注射等量生理盐水,30 d后,分别测定各组大鼠心功能,观察梗死区及其周围心肌病理改变,同时免疫组化和Western-blot方法测定并比较3组大鼠心梗区域心肌细胞核转录因子CHOP蛋白的表达改变。结果 EPO治疗组大鼠心功能较心肌梗死组大鼠明显改善,表现为左室发展压(left ventricular developed pressure,LVDP)值较梗死组大鼠升高,但比假手术对照组低(P<0.01),梗死组心肌纤维化严重,残存心肌排列紊乱,而EPO治疗组可见梗死心肌部位的间质纤维化明显改善。免疫组化和Western-blot显示实验组中核转录因子CHOP蛋白在EPO治疗组表达明显低于心肌梗死组(P<0.05)。结论 EPO可以明显改善心梗大鼠的心功能,其机制可能与抑制核转录因子CHOP的过表达从而抑制内质网应激引起的心肌细胞凋亡有关。
【Abstract】 OBJECTIVE To investigate the inhibition of erythropoietin protection on the expression of transcription factor C/EBP homologous(CHOP) in SD rats with myocardial infarction.METHODS Thirty male SD rats were divided into three groups,including sham operation group,myocardial infarction group and erythropoietin(EPO) treatment group.Myocardial infarction models were developed by ligating the left anterior descending coronary artery.The EPO treatment group was established by injecting recombinant human erythropoietin(rh-EPO)(1 000 u·kg-1) intraperitoneally everyday after operation,and the other two groups were injected with sodium chloride.The intraventricular pressure,pathological changes on infarction area were observed,and the expression of CHOP was also detected by immunohistochemistry and Western Blot analysis after 30 d.RESULTS The heart function in EPO treatment group was improved,compared with myocardial infarction group.Myocardial fibrosis and disorder were improved in EPO treatment group while it was more severe in myocardial infarction group.The expression of CHOP in myocardial infarction group was also more than EPO treatment group.CONCLUSION Erythropoietin could improve heart function in myocardial infarction rats by down-regulating the expression of CHOP,which may protect the survival myocardium,avoid endoplasmic reticulum stress damage and improve the heart function.
【Key words】 erythropoietin; myocardial infarction; C/EBP homologous protein(CHOP);
- 【文献出处】 中国药学杂志 ,Chinese Pharmaceutical Journal , 编辑部邮箱 ,2011年01期
- 【分类号】R542.22
- 【被引频次】11
- 【下载频次】164