中文摘要：

目的观察促红细胞生成素（EPO）对血管紧张素Ⅱ（AngⅡ）诱导培养的乳鼠心脏成纤维细胞（cF）表型转化的影响，以及其可能的信号通路（TGF-β1-TAK1-p38MAPK）在其中的作用。方法体外分离培养乳鼠心脏成纤维细胞，用10μmol／L的Angll诱导培养心脏成纤维细胞表型转化，加入20kU／L的EPO进行预干预，同时加或不加15la,mol／L的SB203580进行处理，以平滑肌肌动蛋白（SMA）表达作为心脏成纤维细胞表型转化的观察指标，应用免疫组织化学观察心脏成纤维细胞内SMA表达情况；采用实时荧光定量PCR方法检测细胞内信号分子转化生长因子β1（TGF-β1）及p38丝裂原活化蛋白激酶（p38MAPK）mRNA的表达情况；采用蛋白免疫印迹法检测α平滑肌肌动蛋白（α-SMA）、TGF-β1、转化生长因子激活性激酶1（TAKl）、p38MAPK以及磷酸化的TAKl（p-TAKl）和p-p38MAPK的表达情况。结果20kU／L的EPO能有效抑制Ang1I诱导的CF细胞表型转化，减少cF细胞内Ct—SMA蛋白的沉积，降低cF表型转化相关信号分子TGF．Bl、p-TAKl、TAKl、p-p38MAPK和p38MAPK的活化或表达，且加入SB203580后该作用增强。结论EPO可抑制AnglI诱导的乳鼠心脏成纤维细胞表型转化为肌成纤维细胞，减轻心肌纤维化，并可降低相关信号分子mRNA及蛋白的表达，初步考虑EPO抑制心肌纤维化，减轻心室重构的作用是通过TGF-β1-TAK1-p38MAPK进行的。

英文摘要：

Aim To observe the effects of erythropoietin （EPO） on neonatal rat cardiac fibrosis phenotypic switched into myofibroblasts induced by angiotensin Ⅱ （ AngⅡ ） and the association with possible signaling pathway （ tran sforming growth factor-beta1 （TGF-β1）-TGF-β1-activated kinase-1 （TAK1）-mitogen-activated protein kinase（p38MAPK） ）. Methods Cardiac fibroblasts were isolated from new-born Sprague-Dawley rats, and the cells were used to establish the model of fibrosis by Ang II （10.6 tool/L） in vitro. Then they were treated with EPO（20 kU/L） ,at the same time,they were treated with or without the p38MAPK inhibitor SB203580 （ 15 I.umol/L）. Immunohistochemistry was used to detect the intraeellular protein expression of α-smooth muscle aetin（cx-SMA）. The mRNA levels of TGF-β1 and p38MAPK was analyzed by quantitative real-time PCR. The protein expression of α-SMA,TGF-β1, TAKI, and p38MAPK and the phos- phorylation of TAK1 and p38MAPK were analyzed by Western blot. Results 20 kU/L of EPO can effectively inhibit Ang II-induced cardiac phenotypie switched into myofibroblasts, reduce the intraeellular protein expression of s-smooth muscle actin （et-SMA）, and also can significantly suppress AngII-induced upregulation of TGF-β1, TAKt, and p38MAPK expression and phosphrylation of TAK1 and p38MAPK. The effects can be strengthened by SB203580. Conclusion EPO can effectively inhibit Ang 1I -induced cardiac phenotypic switched into myofibroblasts, reduce myocardial fibrosis, and can reduce the related signaling molecules mRNA and protein expression. Preliminary consideration of the EPO can inhib- it myocardial fibrosis, reduce the process of ventricular remodeling through TGF-TAKl -p38MAPK.