摘要
目的观察促红细胞生成素(EPO)对新生大鼠心肌细胞肥大中信号通路蛋白表达的影响。方法用血管紧张素Ⅱ(AngⅡ,10-6mol/L)诱导心肌细胞肥大,分别以EPO(2×104U/L)或/和P38丝裂原活化蛋白激酶(MAPK)抑制剂SB203580(15μmol/L)进行干预,检测心肌细胞表面积、蛋白合成、胚胎基因ANF及β-MHC表达,Real-timeQ-PCR检测转化生长因子β(TGF-β)1及P38MAPK mRNA表达;Western blot法检测TGF-β1、TGF-β激活性激酶1(TAK1)、phospho-TAK1、P38MAPK和phospho-P38MAPK蛋白的表达。结果 EPO能有效抑制AngⅡ诱导的心肌细胞肥大(P<0.05),抑制TGF-β1、TAK1、phospho-TAK1、P38MAPK和phospho-P38MAPK表达(P<0.05);SB203580能增强EPO抑制心肌细胞肥大的作用。结论 EPO能减轻AngⅡ诱导的心肌细胞肥大,其可能与TGF-β1-TAK1-P38 MAPK信号通路有关。
Objective To observe the effects of erythropoietin （EPO） on angiotensin Ⅱ （ Ang Ⅱ ） induced neonatal rat cardiomyocyte hypertrophy and its signal protein expression. Methods Cardiomyocytes were isolated from new born Sprague-Dawley rats and were used to establish the model of hypertrophy by AngII in vitro. The cells were trea ted with EPO or/and P38MAPK inhibitor SB203580. The cell surface area size, [ ^3H]-leucine incorporation, mRNA expression of atrial natriuretic factor（ANF） and β-myosin heavy chain （β-MHC） of cardiomyocytes were em ployed as indicators to measure cardiomyocyte hypertrophy. The mRNA levels of TGF-β1 and P38MAPK were ana lyzed by real-time quantitative PCR. The protein expression of TGF-β1 ,TAK1, P38MAPK and phosphorylation of TAK1 and P38MAPK were analyzed by Western blot. Results EPO attenuated hypertrophy of cardiomyocytes. EPO significantly suppressed TGF-β, TAK1, P38MAPK, phosphrylation of TAK1 and P38MAPK expression. SB203580 represses cardiac hypertrophy. Conclusions EPO attenuates cardiomyocytes hypertrophy induced by Ang II,and it is potentially associated with TGF β-TAK1-P38MAPK signaling pathway.
出处
《基础医学与临床》
CSCD
北大核心
2014年第3期295-300,共6页
Basic and Clinical Medicine
基金
国家自然科学基金(30960138)
云南省自然科学基金(2009ZC176M)
