Key Laboratory of Viral Heart Diseases, Ministry of Public Health, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Eur J Pharmacol. 2011 May 11;658(2-3):168-74. doi: 10.1016/j.ejphar.2011.02.040. Epub 2011 Mar 1.
Myocardial fibrosis plays an important role in coxsackievirus B3 (CVB3) induced dilated cardiomyopathy. Excessive transforming growth factor (TGF)-β1 contributes to a pathologic excess of tissue fibrosis. We investigated the effect of astragaloside IV on myocardial fibrosis in CVB3-induced dilated cardiomyopathy. BALB/c mice were inoculated with CVB3 to induce acute viral myocarditis on day 7 (acute VMC group), monthly for 3 months to induce chronic myocarditis (chronic VMC group), and monthly for 9 months to induce dilated cardiomyopathy (DCM group). The same method was used for the DCM+Astra group as that of the DCM group, but former group was given with astragaloside IV-containing drinking water. Compared to DCM group, astragaloside IV treatment significantly increased the survival rate. Histological findings and the collagen volume fraction showed that astragaloside IV decreased fibrosis in heart tissues. Astragaloside IV decreased the level of the serum carboxy-terminal propeptide of procollagen type I (PICP) and the ratio of PICP/ N-terminal type I procollagen propeptide (PINP). Ameliorated myocardial fibrosis was consistent with the downregulated expression of TGF-β1 and its downstream pSmad2/3 and Smad4 in the myocardium of the DCM+Astra group compared to the DCM group. The level of type I collagen was lower in the DCM+Astra group than the DCM group. The same effect was found in the in vitro study. These findings showed that astragaloside IV had a potent preventive effect on myocardial fibrosis in CVB3-induced dilated cardiomyopathy that might be due to downregulation of TGF-β1-Smad signaling.
心肌纤维化在柯萨奇病毒 B3（CVB3）诱导的扩张型心肌病中起着重要作用。过量的转化生长因子（TGF）-β1导致病理性组织纤维化过度。我们研究了黄芪甲苷 IV 对 CVB3 诱导的扩张型心肌病中心肌纤维化的影响。BALB/c 小鼠接种 CVB3 于第 7 天（急性 VMC 组）诱导急性病毒性心肌炎，每月 1 次共 3 个月诱导慢性心肌炎（慢性 VMC 组），每月 1 次共 9 个月诱导扩张型心肌病（DCM 组）。DCM+Astra 组的方法与 DCM 组相同，但前者用含黄芪甲苷 IV 的饮用水治疗。与 DCM 组相比，黄芪甲苷 IV 治疗显著提高了生存率。组织学发现和胶原体积分数表明，黄芪甲苷 IV 减少了心脏组织中的纤维化。黄芪甲苷 IV 降低了血清Ⅰ型前胶原羧基末端肽（PICP）水平和 PICP/N 末端Ⅰ型前胶原原肽（PINP）的比值。与 DCM 组相比，DCM+Astra 组心肌中 TGF-β1及其下游 pSmad2/3 和 Smad4 的表达下调，心肌纤维化得到改善。与 DCM 组相比，DCM+Astra 组Ⅰ型胶原水平较低。体外研究也发现了同样的效果。这些发现表明，黄芪甲苷 IV 对 CVB3 诱导的扩张型心肌病中心肌纤维化具有强大的预防作用，这可能是由于 TGF-β1-Smad 信号通路的下调。
