关键词: 芍药苷, 日本血吸虫, 肝纤维化, α平滑肌肌动蛋白, 转化生长因子β1

Abstract: Objective To investigate the mechanism of paeoniflorin in preventing hepatic granuloma formation and fibrosis in mice infected with Schistosoma japonicum. Methods Model of hepatic granuloma and fibrosis was established by infecting mice with S. japonicum cercariae. The infected mice were randomly divided into 4 groups: group A as model(infected control) group (15 mice), and paeoniflorin being given before, simultaneously and after praziquantel treatment as groups B, C and D. Each of the groups B, C and D was subdivided into 3 subgroups(15 mice each): low dose(paeoniflorin 2 ml, 30 mg/(kg·d)×30 d), high dose(paeoniflorin 2 ml, 120 mg/(kg·d)×30 d) and control (2 ml, 0.5% sodium carboxymethycellulose×30 d). In group B, paeoniflorin or sodium carboxymethycellulose was orally administrated on 12 d after infection. In groups C and D, paeoniflorin or sodium carboxymethycellulose was administrated on 42 d or 72 d after infection. Each of group B, C and D was orally given praziquantel 2 ml (500 mg/(kg·d)×2 d) on 42 d after infection. On the 102nd day after infection, all animals were sacrificed by cervical dislocation. Serum hyaluronic acid (HA) was detected by radioimmunoassay; area of egg granuloma and degree of hepatic fibrosis were observed via HE and Masson stainings; the expression of transforming growth factor β1(TGF-β1), αsmooth muscle actin(α-SMA) and collagenⅠ(ColⅠ) protein were measured by immunohistochemical method. Results In group B, the level of HA (0.719±0.239 μg/ml, 0.721±0.182 μg/ml) in low or high dose subgroups was significantly lower (F=9.429, P＜0.01) than the control subgroup (1.049±0.286 μg/ml); the area of granuloma (0.066±0.005 mm2, 0.064±0.004 mm2) or the degree of hepatic fibrosis (2.067±0.458, 1.967±0.399) in low or high dose subgroups was significantly greater (F=862.540, F=29.738, P＜0.01) than the control (0.141±0.008 mm2, 3.467±0.834); the expression of α-SMA positive cells (2.933±0.594, 3.000±0.535) in low or high dose subgroups was significantly lower(F=12.323, P＜0.01, P＜0.01) than its control (4.800±1.859); the expression of TGF-β1 (0.256±0.057, 0.274±0.054) in low or high dose subgroups was significantly lower (F=148.990, P＜0.01) than its control(0.552±0.047); the content of ColⅠ(0.334±0.041, 0.339±0.042) in low or high dose subgroups was significantly lower (F=180.881, P＜0.01) than its control (0.601±0.049). In groups C & D, no significant difference was found between the low or high dose subgroups or between the subgroups and their corresponding controls. Conclusion Paeoniflorin can significantly reduce hepatic granuloma formation and fibrosis due to schistosome eggs, and decrease the expression of TGF-β1, α-SMA in mice when it is given before praziquantel administration, which may associate with the activation of hepatic stellate cells and the expression of TGF-β1 in liver tissue.

Key words: Paeoniflorin, Schistosoma japonicum, Hepatic fibrosis, α-smooth muscle actin, Transforming growth factor β1