【摘要】 目的利用cTnTR141W转基因扩张型心肌病小鼠,研究人参皂甙Rb1对遗传性扩张型心肌病心功能及心脏重构的作用及其可能机制。方法将cTnTR141W转基因小鼠随机分为模型组和人参皂甙Rb1治疗组(70 mg/kg/d),连续给药7个月,取野生型小鼠作为对照组。心脏超声检测心脏功能及几何构型。HE染色观察心肌细胞变化。透射电镜分析心肌超微结构。RT-PCR检测心肌粘附蛋白的表达。免疫荧光激光共聚焦观察心肌粘附分子Itga8的表达与分布。结果Rb1长期给药能显著改善该模型的心脏功能及几何构型。光镜和透射电镜观察显示Rb1能减轻心肌细胞排列紊乱及超微结构的破坏。RT-PCR结果显示,在模型中Cx40表达降低,E-cad、itga8和itgb1bp3表达升高,但在Rb1组中接近正常水平。免疫荧光激光共聚焦结果显示Rb1可降低Itga8的表达量并调节其分布。结论Rb1可改善扩张型心肌病模型的心功能,抑制心脏重构,其作用可能部分通过调节粘附蛋白的表达而实现的。更多还原

【Abstract】 Objective To study the effects and mechanisms of Rb1 on cardiac function and remodeling of dilated cardiomyopathy in cTnT^R141W transgenic mouse.Methods The αMHC-cTnT^R141W transgenic mice aged 2 months were randomly divided into 2 groups,either drinking water alone as a placebo or Rb1 dissolved in drinking water（70 mg/Kg/d）.Age-matched nontransgenic mice drinking water were used as wild type control.The drug was administered for 7 months.We detected the cardiac function and geometry by echocardiography.Histology and transmission electron microscopy were used to assess myocardial organization and ultrastructure.The expression of adhesion proteins was detected by RT-PCR.Immunofluorescence was performed to examine localization of Itga8.Results We found that ginsenoside-Rb1 significantly improved cardiac function and geometry by long-term administration.Histology and transmission electron microscopy showed that Rb1 attenuated myocardial disarray and ultrastructural abnormality in the cTnT^R141W heart.RT-PCR revealed that the expression of Cx40,E-cad,itga8 and itgb1bp3 were turned over to nearly normal levels in the Rb1 group,while the decreased expression of Cx40 and the increased expression of E-cad,itga8 and itgb1bp3 were detected in the placebo group.Confocal immunofluorescence showed that Rb1 regulated the distribution of Itgα8.Conclusion These findings revealed that Rb1 could improve cardiac function and inhibit cardiac remodeling of DCM in cTnT^R141W transgenic mice,partly through regulating adhesion proteins expression.更多还原