[Effect of astragaloside on myocardial fibrosis in chronic myocarditis].
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 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.


RESULTS
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.


CONCLUSIONS
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.
Zhang
Zhao-cai
ZC
Department of Cardiology, Zhongshan Hospital, Fudan University, Shanghai.
Li
Shuang-jie
SJ
Yang
Ying-zhen
YZ
D000818:Animals; D015153:Blotting, Western; D002908:Chronic Disease; D003384:Coxsackievirus Infections / Q000150:complications; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use; D004719:Endomyocardial Fibrosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D011897:Random Allocation; D012503:Saponins / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014315:Triterpenes / Q000627:therapeutic use*
D004365:Drugs, Chinese Herbal; C507096:Mmp14 protein, mouse; D012503:Saponins; D016212:Transforming Growth Factor beta; D014315:Triterpenes; C052064:astragaloside A; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; D053511:Matrix Metalloproteinase 14