TGF—β1及AngⅡ对大鼠心肌细胞肥大的信号转导通路作用研究

目的：探讨在TGF-β1及AngⅡ分别诱导的大鼠心肌细胞肥大中Smad信号途径中Smad2蛋白的表达。方法：分别建立TGF-β1及AngⅡ诱导的大鼠心肌细胞肥大模型，分为正常对照组、TGF-β1组以及AngⅡ组。以碘化丙啶（PI）染色标记法检测心肌细胞中RNA的表达量以间接反映心肌细胞肥大。以实时荧光定量PCR检测心肌细胞肥大相关肌球蛋白重链β亚型（β—MHC）的表达。以Western blot检测心肌细胞中磷酸化Smad2信号蛋白的表达。结果：TGF-β1及AngⅡ诱导的培养心肌细胞中肥大相关蛋白β1-MHC的表达均明显高于对照组（P〈0．01）。PI染色检测表明，TGF-β1组及AngⅡ组PI的含量明显增高（P〈0．01）。与对照组相比，TGF-β1及AngⅡ均可明显上调磷酸化Smadz（p-Smad2）的表达（P〈0．01）。TGF-β1组与AngⅡ组p-Smad2表达峰值相比无明显差异，但达峰的时间有所不同。结论：TGF-β1及AngⅡ单独均可诱导心肌细胞肥大，在此过程中p-Smad2蛋白的表达明显增加，TGF-β1与AngⅡ促进p-Smad2蛋白表达作用无明显差异。

Study on Smad signal pathway of cardiomyocyte hypertrophy induced by TGF-β1 or AngⅡ in rats

AIM： To explore the mechanism of TGF-β1 or AngⅡ activated cardiomyocyte hypertrophy in regard to Smadpathway. METHODS： Fresh isolated neonatal rat cardiomyocytes induced by normal, TGF-β1 and AngⅡ groups were used to examine the formation of cell pathway, p-Smad2 protein was measured by Western blot. Hypertrophy was measured by PI staining and RNA expressions were detected by real-time PCR. RESULTS： TGF-β1 and AngⅡ induced cardiomyocyte hypertrophy and Smad protein in cardiomyocytes was stimulated by TGF-β1 or AngⅡ. Expression of β-MHC was obviously higher than that in the control group （ P 〈 0. 01 ）. PI staining of TGF-β1 group and AngⅡ group were significantly increased compared with the control group （P 〈 0. 01 ）. Compared with the control group, p-Smad2 proteins in cardiomyocytes were stimulated by TGF-β1 or AngⅡ. In the TGF-β1 group and AngⅡ group there were no significant differences in the peak time. CONCLUSION： TGF-β and AngⅡ activate the Smad signaling system in cardiomyocyte hypertrophy in vitro.