Prevention of Cardiac9 Remodeling and Diastolic Dysfunction by inhibiting Fibrotic Process.

过度的心肌纤维化损害高血压心脏的心功能。研究了转化生长因子(TGF)-B在超载大鼠心肌重构和心功能障碍中的作用。Wistar大鼠肾上主动脉收缩引起压力过载。第3天观察到成纤维细胞活化（增殖和表型向肌成纤维细胞转变），第3-7天达到高峰。第28天心肌细胞肥大，心肌纤维化。第28天，超声心动图显示左室分数缩短正常，但经多普勒速度早、晚充盈比降低，血流动力学测量显示左室舒张末压升高，提示收缩功能正常，舒张功能异常。第3天诱导心肌TGF-B mRNA表达，第7天达到峰值，第28天保持适度升高。术前1天每天腹腔注射抗tgf - b中和抗体（NAb），可抑制成纤维细胞活化，随后阻止胶原mRNA诱导和心肌纤维化，但不能阻止心肌细胞肥大。NAb逆转舒张功能不影响血压和收缩功能。TGF-B通过成纤维细胞激活在心肌纤维化和舒张功能障碍中起因果作用

Excessive myocardial fibrosis impairs cardiac function in hypertensive hearts. Roles of transforming growth factor (TGF)-B in myocardial remodeling and cardiac dysfunction were examined (in press)ure-overloaded rats.Pressure overload was induced by a suprarenal aortic constriction in Wistar rats. Fibroblast activation (proliferation and phenotype transition to myofibroblasts) was observed after day 3 and peaked at days 3-7. Thereafter, myocyte hypertrophy and myocWdial fibrosis developed by day 28. At day 28, echocardiography showed normal LV fractional shortening but the decreased early to late filling ratio of the transmitral Doppler velocity, and hemodynamic measurement revealed LV end-diastolic pressure elevation, indicating normal systolic but abnormal diastolic function. Myocardial TGF-B mRNA expression was induced after day 3, peaked at day 7, and remained modestly increased at day 28.An anti-TGF-B neutralizing antibody (NAb), which was intraperitoneally administered daily from 1 day before operation, inhibited fibroblast activation and subsequently prevented collagen mRNA induction and myocardial fibrosis, but not myocyte hypertrophy. NAb reversed diastolic dysfunction without affecting blood pressure and systolic function.TGF-B plays a causal role in myocardial fibrosis and diastolic dysfunction through fibroblast activation in