目的 探讨鳖甲煎丸抗肝纤维化的作用机制。方法 SD大鼠随机分成6组：对照组，模型组，秋水仙碱（0.1 mg/kg）阳性对照组，鳖甲煎丸低、中、高剂量（0.55、1.1、2.2 g/kg）组。除对照组外，其他各组大鼠sc 40% CCl₄橄榄油溶液，每周2次，连续给予6周，建立大鼠肝纤维化模型。在造模同时，各给药组每天给予相应药物10 mL/(kg?d) 1次，连续给药11周。于11周末处死大鼠，免疫组化法检测肝组织中α-平滑肌肌动蛋白（α-SMA）的表达，反转录聚合酶链反应（RT-PCR）法检测大鼠肝组织中转化生长因子（TGF-β₁）及smad 3基因的表达。结果 与对照组比较，模型组大鼠肝组织α-SMA蛋白及TGF-β₁、smad 3基因的表达显著上调（P＜0.05）。与模型组比较，鳖甲煎丸和秋水仙碱可显著降低大鼠肝组织α-SMA蛋白及TGF-β₁、smad 3基因的表达，其中以鳖甲煎丸2.2 g/kg的效果更显著。结论 鳖甲煎丸抗肝纤维化作用机制可能与其下调TGF-β₁/smad 3信号通路、抑制肝星状细胞活化和增殖有关。

Objective To observe the anti-fibrotic mechanism of Biejiajian Pill. Methods SD rats were randomly divided into six groups: control, model, colchicina (0.1 mg/kg, positive), Biejiajian Pill (0.55, 1.1, and 2.2 g/kg) groups. Except for the control group, the rats in the other groups were sc injected with 40% CCl₄ olive oil solution twice a week for consecutive six weeks to establish the models of liver fibrosis.. At the same time, drugs were ig administrated at a volume of 10 mL/kg in each group, once daily for consecutive 11 weeks. At the end of the week 11, all rats were sacrificed. The immunohistochemical technique was applied to analyzing the expression of α-smooth muscle actin (α-SMA) in liver tissue, RT-PCR was applied to analyzing the expression of transforming growth factor-β₁ (TGF-β₁) protein and smad 3 gene in liver tissue. Results Compared with the control group, the expression levels of α-SMA, TGF-β₁, and smad 3 gene increased significantly (P < 0.05) in the model group. Compared with the model group, Biejiajian Pill and colchicina decreased the expression of α-SMA, TGF-β₁ and smad 3 gene, the efficacy of high-dose Biejiajian Pill group was more significantly. Conclusion The antifibrotic mechanism of Biejiajian Pill may be through lowing the TGF-β₁/smad 3 signaling pathways and inhibiting hepatic stellate cells activation and proliferation.

河北省自然科学基金资助项目（C2009001143）