栀子柏皮汤不同配伍对四氯化碳诱导肝纤维化小鼠的治疗作用

Therapeutical effects of Zhizi Bopi Decoction and its compatibility on CCl_4 induced hepatic fibrosis in mice

目的研究栀子柏皮汤不同配伍组合的抗肝纤维化药理作用。方法采用四氯化碳(CCl_4)引起的肝纤维化小鼠模型观察栀子柏皮汤各配伍组的抗肝纤维化作用,同时给予不同配伍的栀子柏皮汤进行灌胃治疗。生化检测相关肝纤维化及炎症指标,运用Masson染色和HE染色检测肝纤维化的变化,Western blot法检测Ⅰ型胶原及α-横纹肌肌节肌动蛋白(α-SMA)的表达水平。结果栀子柏皮汤及各配伍组均可不同程度的降低小鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、羟脯氨酸(Hyp)及透明质酸(HA)水平,改善肝脏的病理变化,其中栀子黄柏甘草配伍组抑制CCl_4诱导的小鼠肝纤维化效果最佳(P<0.01),并能显著抑制肝组织中Ⅰ型胶原和α-SMA的蛋白表达(P<0.01)。实验结果表明栀子柏皮汤亦可明显降低血清中转化生长因子β(TGF-β)的表达水平。结论栀子柏皮汤不同配伍组能不同程度改善小鼠肝纤维化,但栀子黄柏甘草配伍,即全汤组抗肝纤维化作用最明显,并且栀子柏皮汤的抗肝纤维化作用可能与降低TGF-β水平有关。

Objective To study the anti-hepatofibrotic effects of Zhizi Bopi Decoction and its compatibility on liver fibrosis. Methods The model of mouse liver fibrosis which was induced by carbon tetraehlofide （CC14） was used to investigate the effects of Zhizi Bopi Decoction and its compatibility by gavage. Indicators of hepatic fibrosis and inflammation were detected with automated biochemistry analyzer and liver fibrosis of the mice was assessed by Mas- son staining and HE staining. Meanwhile, the protein levels of collagen type I and α-smooth muscle actin （α- SMA） were evaluated by Western blot analysis. Results Zhizi Bopi Decoction and each different treatment group could evidently inhibit the increased serum alanine aminotransferase （ALT）, aspartate aminotransferase （AST）, hydroxyproline （Hyp） and hyaluronie acid （HA） activities, and improve the pathological changes of mouse livers. Furthermore, the therapeutic effects on liver fibrosis induced by CC14 in mice were primarily ascribed to the syner- gie effect of Gardenia jasminoides Ellis, Cortex phellodendri and Glycyrrhizae Radix et Rhizoma （ P 〈 0. 01 ）. And they could obviously reduce the protein expression levels of collagen type I and α-SMA in the liver （ P 〈 0. 01 ）. In addition, Zhizi Bopi Decoction could also obviously reduce the contents of transforming growth factor-beta （TGF-β）. Conclusion Zhizi Bopi Decoction and its compatibility all perform significant anti-fibrotie effects on the liver in different degree, but the compatibility of Gardenia jasminoides Ellis, Cortex phellodendri and Glycyrrhizae Radix et Rhizoma exert the most distinctly anti-fibrotic effects among them, possibly by reducing the contents of TGF-β.