Zhang Zhao-cai, Li Shuang-jie, Yang Ying-zhen
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2007 Aug;27(8):728-31.
To investigate the effect of astragaloside (Astr), one of the active components of the Chinese medical herb Astragulus membranaceus, on cardiac fibrosis in chronic myocarditis and its relevant mechanisms.
Eighty mice were randomized into 3 groups, the control group (n=20), the model group (n=30) and the Astr group (n=30). Mice in the model group and the Astr group were monthly intraperitoneally inoculated with CVB3, but to the control group equal amount of culture fluid was given instead. Mice in the control and the model group were fed with drinking water while those in the Astr group with drinking water containing Astr-sodium carboxymethycellulose at a concentration of 300 mg/L. All the survived mice were sacrificed 3 months later. Heart tissue of mice was stained by picrosirius red for calculating collagen volume fraction (CVF) with an automatic image analysis system. Expressions of transforming growth factor beta1 (TGF-beta1), platelet derived growth factor (PDGF), matrix metalloproteinase 1 (MMP-1), tissue inhibitor of metalloproteinase 1 (TIMP-1), MMP-13 and MMP-14 in heart tissue were detected by Western blot analysis.
As compared with the model group, in the Astr group, the mortality and CVF were significantly lower (53.3% vs. 23.3%, chi2 = 4.23, P < 0.05), and (17.4 +/- 1.2% vs. 8.6 +/- 0.9%, chi2 = 5.38, P < 0.05), respectively. As compared with the control group, Western blot analysis showed that expression of TGF-beta1 was decreased, MMP-1 and TIMP-1 were down-regulated, while expressions of MMP-13 and MMP-14 were up-regulated after Astr treatment.
Astr could lower the mortality and alleviate the myocardial fibrosis of mice with chronic myocarditis. Its antifibrotic effect might be realized by way of inhibiting TGF-beta1 expression and up-regulating the expressions of MMP-13 and MMP-14 in the heart tissues.
研究中药黄芪的活性成分之一黄芪皂苷(Astr)对慢性心肌炎心肌纤维化的影响及其相关机制。
将80只小鼠随机分为3组,即对照组(n = 20)、模型组(n = 30)和Astr组(n = 30)。模型组和Astr组小鼠每月腹腔注射柯萨奇病毒B3(CVB3),对照组注射等量培养液。对照组和模型组小鼠饮用普通水,Astr组小鼠饮用含300 mg/L黄芪皂苷-羧甲基纤维素钠的水。3个月后处死所有存活小鼠。用天狼星红对小鼠心脏组织进行染色,通过自动图像分析系统计算胶原容积分数(CVF)。采用蛋白质免疫印迹法检测心脏组织中转化生长因子β1(TGF-β1)、血小板衍生生长因子(PDGF)、基质金属蛋白酶1(MMP-1)、金属蛋白酶组织抑制剂1(TIMP-1)、MMP-13和MMP-14的表达。
与模型组相比,Astr组小鼠死亡率和CVF均显著降低,分别为(53.3% 对 23.3%,χ2 = 4.23,P < 0.05)和(17.4 ± 1.2% 对 8.6 ± 0.9%,χ2 = 5.38,P < 0.05)。蛋白质免疫印迹分析显示,与对照组相比,Astr处理后TGF-β1表达降低,MMP-1和TIMP-1表达下调,而MMP-13和MMP-14表达上调。
Astr可降低慢性心肌炎小鼠死亡率,减轻心肌纤维化。其抗纤维化作用可能通过抑制心脏组织中TGF-β1表达及上调MMP-13和MMP-14表达来实现。