基于Wnt/β-catenin 信号通路探讨双术抗纤方（黄芪、麸炒白术、柴胡、醋莪术、丹参、荔枝核） 改善四氯化碳（CCl4）诱导大鼠肝纤维化的作用及机制。方法采用皮下注射3.0 mL·kg-1 质量分数为40% 的 CCl4 复制肝纤维化大鼠模型，每周注射2 次，共注射8 周。将SD 大鼠随机分为空白对照组（8 只）、模型组 （7 只）、阳性对照组（7 只，灌胃43.19 mg·kg-1 水飞蓟宾）、中药低剂量组（6 只，灌胃4.3 g·kg-1 双术抗纤方颗 粒）、中药中剂量组（6 只，灌胃8.6 g·kg-1 双术抗纤方颗粒）、中药高剂量组（7 只，灌胃17.2 g·kg-1 双术抗纤方 颗粒）；每日1 次，连续灌胃给药4 周，除空白对照组外，余各组在给药同时继续皮下注射CCl4。采用HE、 Masson 染色法观察肝脏组织病理变化；ELISA 法检测血清Ⅳ型胶原（Col Ⅳ）、Ⅲ型前胶原（PC Ⅲ）、透明质酸 （HA）、层粘连蛋白（LN）水平；Western Blot 法检测肝脏组织Wnt1、β-catenin、PPAR-γ 蛋白表达水平；qPCR 法检测肝脏组织Wnt1、β-catenin、PPAR-γ mRNA 表达水平。结果与空白对照组比较，模型组大鼠肝脏出 现肝细胞部分坏死，正常的肝小叶结构被破坏，肝细胞索排列紊乱，中央静脉或汇管区增大，炎症细胞大量浸 润，形成桥接坏死；肝脏中央静脉或汇管区胶原纤维增生明显，形成纤维间隔，纤维化评分明显升高（P＜ 0.05）；血清Col Ⅳ、PCⅢ、HA、LN 水平明显升高（P＜0.05）；肝脏组织Wnt1、β-catenin 蛋白及mRNA 表达 水平明显升高（P＜0.05），PPAR-γ 蛋白及mRNA 表达水平明显降低（P＜0.05）。与模型组比较，阳性对照组以 及中药中、高剂量组大鼠肝细胞脂肪变性情况有所改善，坏死、炎性细胞浸润减少；肝脏纤维化程度有所改 善，肝脏胶原纤维减少，纤维化评分明显降低（P＜0.05）；血清ColⅣ、PCⅢ、HA、LN 水平明显降低（P＜ 0.05）；肝脏组织Wnt1、β-catenin 蛋白及mRNA 表达水平明显降低（P＜0.05），PPAR-γ 蛋白及mRNA 表达水 平明显升高（P＜0.05）。结论双术抗纤方有抗CCl4 诱导大鼠肝纤维化的作用，其机制可能与抑制Wnt/β- catenin 信号通路及上调PPAR-γ 表达有关。

To investigate the effect and mechanism of Shuangzhu Kangxian Prescription（Astragali Radix， bran-fried Atractylodis Macrocephalae Rhizoma， vinegar-prepared Rhizoma Curcumae， Bupleuri Radix， Salviae Miltiorrhizae Radix et Rhizoma， Litchi Semen）on improving hepatitic fibrosis induced by carbon tetrachloride （CCl4） in rats based on the Wnt/β-catenin signaling pathway. Methods The rat model of hepatitic fibrosis was replicated by subcutaneous injection of 3.0 mL·kg-1 40% CCl4 twice a week for 8 weeks. SD rats were randomly divided into blank control group （n=8）， model group （n=7）， positive control group （n=7， intragastric administration of 43.19 mg·kg-1 silymarin），low-dose Chinese medicine group （n=6，intragastric administration of 4.3 g · kg-1 Shuangzhu Kangxian Prescription）， medium-dose Chinese medicine group （n=6， intragastric administration of 8.6 g · kg-1 Shuangzhu Kangxian Prescription）， high-dose Chinese medicine group （n=7， intragastric administration of 17.2 g · kg-1 Shuangzhu Kangxian Prescription） . The continuous intragastric administration was given once a day for 4 consective weeks，in addition to the blank control group，the other groups continued to be subcutaneously injected with CCl4 at the same time. The pathological changes of liver tissue were observed by HE and Masson staining. The levels of serum type IV collagen （Col IV），type Ⅲ procollagen （PCIII）， hyaluronic acid （HA） and laminin （LN） were detected by ELISA. The protein expression levels of Wnt1， β- catenin and PPAR-γ in liver tissue were detected by Western Blot. The mRNA expression levels of Wnt1， β- catenin and PPAR-γ in liver tissue were detected by qPCR. Results Compared with the blank control group，the liver of the model group showed partial necrosis of liver cells， the normal hepatic lobule structure was destroyed， the arrangement of liver cell cords was disordered，the central vein or portal area was enlarged，and a large number of inflammatory cells infiltrated to form bridging necrosis. The collagen fibers in the central vein or portal area of the liver proliferated significantly， forming fibrous septa， and the fibrosis score were significantly increased （P＜ 0.05） . The levels of serum Col IV，PCⅢ，HA and LN were significantly increased （P＜0.05） . The protein and mRNA expression levels of Wnt1 and β-catenin in liver tissue were significantly increased （P＜0.05）， and the protein and mRNA expression levels of PPAR-γ were significantly decreased （P＜0.05） . Compared with the model group，the steatosis of hepatocytes in the positive control group and the medium- and high- dose groups of Chinese medicine was improved， and the necrosis and inflammatory cell infiltration were reduced. The degree of hepatitic fibrosis was improved，the liver collagen fibers were reduced，and the fibrosis score was significantly reduced （P＜ 0.05） . The levels of serum Col IV，PCⅢ，HA and LN were significantly decreased （P＜0.05） . The protein and mRNA expression levels of Wnt1 and β-catenin in liver tissue were significantly decreased （P＜0.05）， and the protein and mRNA expression levels of PPAR-γ were significantly increased （P＜0.05） . Conclusion Shuangzhu Kangxian Prescription has the effect of anti CCl4-induced hepatitic fibrosis in rats， and its mechanism may be related to the inhibition of Wnt/β-catenin signaling pathway and up-regulation of PPAR-γ expression.

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国家自然科学基金项目（82160834）；2022年全国名老中医药专家传承工作室建设项目[国中医药人教函（2022）75号]；广西研究生教育 创新计划资助项目（YCBXJ2021021）。