人参皂甙Rb1抑制扩张型心肌病发生中的HB-EGF表达和纤维化

目的HB-EGF过表达可促进心肌纤维化及心肌细胞凋亡,本文研究人参皂甙Rb1对cTnT^R141W转基因扩张型心肌病小鼠发病过程中的HB-EGF表达和心肌纤维化的影响。方法将cTnT^R141W转基因小鼠随机分为模型组和人参皂甙Rb1组（70 mg/kg/d）,连续给药7个月,取野生型小鼠作为对照组。用Kaplan-Meier法进行生存分析。心脏超声检测心功能及心脏几何构型。计算心重指数。光镜观察心肌细胞及间质变化。Western blot检测心脏HB-EGF,pSTAT3表达水平。结果Rb1长期给药能显著改善该模型的心功能和心脏几何构型,将死亡率降低50%。Rb1治疗组心重指数降低11.3%（P〈0.05）,光镜观察显示Rb1能减轻心肌细胞排列紊乱以及间质纤维化。Western blot结果显示Rb1能够显著降低模型中的HB-EGF及pSTAT3的表达。结论Rb1抑制心肌病发生中的HB-EGF表达及抑制下游信号pSTAT的激活,并改善扩张型心肌病模型的心功能及心脏重构。

Ginsenoside-Rbl Inhibits the HB-EGF Expression and Fibrosis during Development of Dilated Cardiomyopathy in cTnT^R141W Transgenic Mouse

Objective To investigate the effects of Rbl on the expression of HB-RGF and cardiac remodeling during development of dilated cardiomyopathy in the eTnT^R141w transgenic mouse. The HB-EGF mediates the remodeling of heart and increases the cardiofibrosis and cardiomyocyte apoptosis. Methods The αMHC-cTnT^R141W transgenic mice aged 2 months were randomly divided into 2 groups, either drinking water alone as a placebo or Rbl dissolved in drinking water （70 mg/Kg/d）. Agematched nontransgenic mice drinking water were used as wild type control. The drug was administered for 7 months. The cardiac function was analyzed by echocardiography. Histology was used to assess myocardial interstitial fibrosis in the heart. The expression of HB-EGF, pSTAT3 and STAT3 were detected by western blot. Results We found that long-term administration of ginsenoside-Rb1 significantly improved cardiac function and reduced mortality by 50% . The HW/BW ratio of Rb1-treated mice was significantly lower than that of placebo mice （11.3%, P 〈 0.05）. Histological analysis showed that Rbl attenuated the myocardial disarray, decreased the interstitial fibrosis in the cTnT^R141w heart. Western blot analysis indicated that Rbl treatment significantly downregulated HB-EGF and pSTAT3 expression, which were steadily overexpressed in the placebo mice. Conclusion These findings revealed that Rbl downregulated the HB-EGF expression and STAT3 activation during development of dilated cardiomyopathy in the cTnT^R141W transgenic mouse so as to relieve cardiac remodeling and improve heart function.