【摘要】 目的：观察补肝健膝方对膝骨关节炎模型兔软骨Wnt信号通路的影响。方法：将36只新西兰兔随机分为正常组、模型组、阳性药物组、补肝健膝方低剂量组、补肝健膝方中剂量组、补肝健膝方高剂量组，每组各6只。采用木瓜蛋白酶关节腔注射方法制备兔膝骨关节炎模型，造模成功后，补肝健膝方低、中、高剂量组兔予相应剂量补肝健膝方灌胃，阳性药物组兔予独活寄生汤灌胃。正常组、模型组兔予等量生理盐水灌胃。给药4周后，采用ELISA法检测关节液白细胞介素（IL-1）、肿瘤坏死因子-α(TNF-α)的表达水平，取关节软骨及滑膜进行大体观察和光镜下显微形态观察，采用Western blotting法检测软骨组织Wnt3a、β-catenin、MMP-13蛋白相对表达量。结果：HE染色和大体观察显示补肝健膝方能减轻软骨退行性变，对软骨具有保护作用。模型组兔关节液中IL-1、TNF-α水平高于正常组（P<0.01），阳性药物组、补肝健膝方低剂量组、补肝健膝方中剂量组、补肝健膝方高剂量组兔关节液IL-1、TNF-α水平均低于模型组（P<0.01）。模型组兔关节软骨Wnt3a、β-catenin、MMP-13蛋白相对表达量高于正常组（P<0.01），补肝健膝方高剂量组兔关节软骨Wnt3a蛋白相对表达量低于模型组（P<0.05）。阳性药物组、补肝健膝方低剂量组、补肝健膝方中剂量组、补肝健膝方高剂量组兔关节软骨β-catenin蛋白相对表达量与模型组比较，差异无统计学意义（P>0.05）。阳性药物组、补肝健膝方中剂量组、补肝健膝方高剂量组兔关节软骨MMP-13蛋白相对表达量均低于模型组（P<0.05）。结论：补肝健膝方能抑制兔膝骨关节炎模型软骨Wnt信号通路，从而减轻炎症反应，维持细胞外基质的完整性，改善膝骨关节炎模型中的软骨形态。更多还原

【Abstract】 Objective: To investigate the effects of Bugan Jianxi formula on Wnt/β-catenin signaling pathway of cartilage in rabbits with knee osteoarthritis model. Methods: Totally 36 New Zealand rabbits were randomly divided into normal group, model group, positive drug group, low-dose group, medium-dose group and high-dose group, 6 rabbits in each group. Rabbit model of knee osteoarthritis was established according to papain intra-articular injection method. After successful molding, rabbits were given corresponding dosage of Bugan Jianxi formula respectively in low-dose, medium-dose and high-dose groups, and Duhuo Jishen decoction in positive drug group. Rabbits were given equal doses normal saline in normal group and model group. The serum and joint fluid were extracted to detect IL-1 and TNF-α expression by ELISA, and the right knee cavity was opened for articular cartilage and synovial gross observation and microscopic observation in 4 weeks. The expression of Wnt 3a,β-catenin, and MMP-13 protein in rabbit cartilage were detected by Western blotting method. Results:According to HE staining and gross observation, Bugan Jianxi formula can alleviate cartilage degeneration, with protective effect on cartilage. The model group showed higher levels of IL-1 and TNF-α in joint fluid than normal group(P<0.01). The positive drug group, low-dose group, medium-dose group and high-dose group showed lower levels of IL-1 and TNF-α in joint fluid than model group(P<0.01). The model group showed higher relative expressions of Wnt3a, β-catenin and MMP-13 proteins than normal group(P<0.01). The high-dose group showed lower relative expressions of Wnt3a protein than model group(P <0.05). There was no statistically significant differences in relative expressions of β-catenin protein among positive drug group, low-dose group, medium-dose group and model group(P>0.05). The positive drug group, medium-dose group and high-dose group showed lower relative expressions of MMP-13 protein than model group(P<0.05). Conclusion: Bugan Jianxi formula can inhibit the Wnt signaling pathway, thereby reducing inflammatory responses, maintaining the integrity of the extracellular matrix, and improving the cartilage morphology in rabbit model of osteoarthritis.更多还原