Abstract: OBJECTIVE: To investigate the inhibitory effect of chrysanthemum extract on myocardial fibrosis in rats with renovascular hypertension, and explore the possible mechanism underlying this effect.METHODS: Sixty Wistar rats were randomly divided into six groups: sham operation, model, positive control, and low-, medium-, and high-dose Huai chrysanthemum extract groups(ten rats per group). With the exception of the sham operation group, a renal hypertensive model was established in rats using the "two-kidney, one clip" method. After 6 weeks, low-, medium-, and high-dose groups were intragastrically administered chrysanthemum extract at 1, 2, or 4 g/kg, respectively, once daily for 4 weeks. The positive control group was administered Kato Pury at 50 mg/kg once daily for 4 weeks,while sham operation and model groups received an equal volume of distilled water once daily for 4 weeks. Blood pressure changes were examined before modeling, 6 weeks after modeling, and after 4 weeks of treatment administration. Ventricular remodeling indexes were measured by high frequency echocardiography after 4 weeks of treatment administration. Pathological changes were observed by hematoxylin and eosin, and Masson's trichrome staining methods. Collagen type sion were eⅠxa(Col minedⅠ) and type Ⅲ(Col Ⅲ) expres by enzyme-linked immunosorbent assays. Transforming growth factor-β1(TGF-β1), sma mad 3(Smad3),Smad7, Ras homolog gene family, member A(RhoA), and Rho-associated protein kinase 1(ROCK1) protein expression were detected by Western blot.RESULTS: Compared with the model group, chrysanthemum-administered groups and the positive control group showed significant improvement of arterial blood pressure, echocardiography indicators, and degree of myocardial fibrosis(P < 0.05). In addition, these groups exhibited decreased expression of Col Ⅰ, Col Smad3, and increaseⅢ, RhoA, ROCK1, TGF-β1, and d Smad7 expression. Such improvements were most obvious in the high-dose chrysanthemum extract group(P < 0.05).CONCLUSION: Chrysanthemum extract could effectively reduce myocardial fibrosis in rats with renovascular hypertension by a mechanism that potentially involves inhibition of RhoA/ROCK1 and TGF-β1/Smad signaling pathways.

Key words: Chrysanthemum, Hypertension,renovascular, Fibrosis, Ventricular remodeling, Transforming growth factor beta