黄芪甲甙对慢性心肌炎心肌纤维化的影响

Effect of Astragaloside on Myocardial Fibrosis in Chronic Myocarditis

目的探讨中药黄芪的活性成分黄芪甲甙对慢性心肌炎心肌纤维化的影响及其相关机制。方法80只Balb/c小鼠随机分为3组,分别为空白对照组(对照组,20只)、慢性心肌炎组(模型组,30只)和黄芪甲甙干预心肌炎组(干预组,30只)。模型组和干预组小鼠每月1次腹腔接种柯萨奇病毒B3(CVB3),对照组腹腔注射等量病毒培养液。对照组和模型组小鼠每日以饮用水喂养,干预组小鼠以加有羧甲基纤维素钠助溶的黄芪甲甙饮用水(浓度300mg/L)喂养。3个月后处死所有存活小鼠,小鼠心脏组织经苦味酸天狼星红染色后以自动图像分析系统计算胶原容积积分(CVF),以Westernblot方法检测各组小鼠心脏组织中转化生长因子β1(TGF-β1)、血小板衍生生长因子BB(PDGF-BB)、基质金属蛋白酶1(MMP-1)及其组织抑制物(TIMP-1)、MMP-13和MMP-14的表达情况。结果黄芪甲甙干预后,与模型组比较,小鼠死亡率降低(53.3%、23.3%,χ2=4.23,P<0.05)、心脏CVF明显下降〔模型组为(17.4±1.2)%、干预组为(8.6±0.9)%,χ2=5.38,P<0.05〕;与对照组比较,TGF-β1、MMP-1和TIMP-1表达减少而MMP-13和MMP-14的表达增多。结论黄芪甲甙可以降低慢性心肌炎小鼠死亡率、减轻其心肌纤维化,其抗纤维化作用是通过抑制TGF-β1、促进MMP-13和MMP-14在心脏中的表达而实现。

Objective 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. Methods 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 β1 （TGF-β1）, 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. Results As compared with the model group, in the Astr group, the mortality and CVF were significantly lower （53.3% vs 23.3%,;（2=4.23,P〈0.05）, and （17.4±1.2% vs 8.6±0.9%, χ^2 =5.38,P〈0.05） respectively. As compared with the control group, Western blot analysis showed that expression of TGF-β1 was decreased, MMP-1 and TIMP-1 were down-regulated, while expressions of MMP-13 and MMP-14 were up-regulated after Astr treatment. Conclusion 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-β1 expression and up-regulating the expressions of MMP-13 and MMP-14 in the heart tissues.