来源：风湿病与关节炎,2021,10（3）:1-5,15.

寒痹康汤对胶原诱导性关节炎大鼠Wnt/β-catenin和BMP/Smad信号通路的影响（基础研究）

庞学丰，李玉玲，吴燕红，冯玉青，刘　欢，蒙宇华，黄政治，林　菊，吴伟泳，马　静，廖家瑜，王思思

　　【摘　要】目的：观察寒痹康汤对胶原诱导性关节炎（CIA）大鼠Wnt/β-连环蛋白（Wnt/β-catenin）和骨形态发生蛋白/Smad（BMP/Smad）信号通路的影响。方法：采用牛Ⅱ型胶原蛋白和弗氏不完全佐剂充分混合乳化制成CⅡ乳剂，进行皮下注射成功造模CIA大鼠模型，予灌服甲氨蝶呤作为对照，观察寒痹康汤高、中、低剂量提取物对CIA大鼠关节肿胀指数，以及Wnt/β-catenin和BMP/Smad信号通路相关蛋白表达的影响。结果：治疗4周后，各治疗组大鼠关节肿胀指数与模型对照组比较，差异有统计学意义（P < 0.01）。寒痹康汤高剂量组与甲氨蝶呤组比较，差异有统计学意义（P < 0.01）；寒痹康汤中、低剂量组与甲氨蝶呤组比较，差异无统计学意义（P > 0.05）。与空白对照组比较，模型对照组Wnt5α、Wnt7α蛋白表达升高，差异有统计学意义（P < 0.05）；与模型对照组比较，甲氨蝶呤组和寒痹康汤高、中、低剂量组Wnt5α、Wnt7α蛋白表达降低，差异有统计学意义（P < 0.01）；寒痹康汤高、中剂量组与甲氨蝶呤组Wnt5α、Wnt7α蛋白表达比较，差异无统计学意义（P > 0.05）。与空白对照组比较，模型对照组β-catenin、BMP-2、BMP-4、BMP-5、Smad4、Smad5、Smad7蛋白表达升高，差异有统计学意义（P < 0.05）。与模型对照组比较，甲氨蝶呤组和寒痹康汤高、中、低剂量组上述蛋白表达降低，差异有统计学意义（P < 0.05）；寒痹康汤高、中剂量组与甲氨蝶呤组上述蛋白表达比较，差异无统计学意义（P > 0.05）。结论：寒痹康汤可以通过调节Wnt/β-catenin和BMP/Smad信号通路达到治疗类风湿关节炎及抗骨侵蚀的作用。

　　【关键词】　胶原诱导性关节炎；类风湿关节炎；寒痹康汤；Wnt/β-连环蛋白；骨形态发生蛋白/Smad；信号通路；大鼠

Effect of Hanbikang Tang（寒痹康汤）on Wnt/β-catenin and BMP/Smad Signaling Pathway in Collagen Induced Arthritis Rats

PANG Xue-feng,LI Yu-ling,WU Yan-hong,FENG Yu-qing,LIU Huan,MENG Yu-hua,HUANG Zheng-zhi,LIN Ju,WU Wei-yong,MA Jing,LIAO Jia-yu,WANG Si-si

　　【ABSTRACT】Objective:To observe the effect of Hanbikang Tang（寒痹康汤）on Wnt/β-catenin and BMP/Smad signaling pathway in collagen induced arthritis（CIA）rats.Methods:CⅡ emulsion was prepared by mixing bovine type Ⅱ collagen and Freund's incomplete adjuvant.The CIA rat model was successfully established by subcutaneous injection,and methotrexate was given to establish the control.The effects of high,medium and low dose extracts of Hanbikang Tang on joint swelling index and expressions of Wnt/β-catenin and BMP/Smad signaling pathway related proteins in CIA rats were observed.Results:After 4 weeks treatment,the difference of the joint swelling index between each treatment group and the model control group was statistically significant（P < 0.01）,among which the difference between the high-dose Hanbikang Tang group and the methotrexate group was statistically significant（P < 0.01）,and the difference between the middle and low dose Hanbikang Tang group and the methotrexate group was not statistically significant（P > 0.05）.Compared with the blank control group,the protein expression of wnt5α and wnt7α in the model control group increased,and the difference was statistically significant（P < 0.05）;compared with the model control group,the protein expression of wnt5α and wnt7α in the methotrexate group,the high,medium and low dose Hanbikang Tang groups decreased,and the difference was statistically significant（P < 0.05）.There was no significant difference in the protein expression of wnt5α and wnt7α between the high and medium dose Hanbikang Tang groups and the methotrexate group（P > 0.05）.Compared with the blank control group,the protein expressions of β-catenin,BMP-2,BMP-4,BMP-5,Smad4,Smad5 and Smad7 in the model control group was increased,and the difference was statistically significant（P < 0.05）;compared with the model control group,the above protein expressions of the methotrexate group and the high,medium and low dose Hanbikang Tang groups were decreased,and the difference was statistically significant（P < 0.05）.There was no significant difference in the above protein expressions between the high and medium dose Hanbikang Tang groups and methotrexate group（P > 0.05）.Conclusion:Hanbikang Tang can treat rheumatoid arthritis and resist bone erosion by regulating Wnt/β-catenin and BMP/Smad signaling pathways.

　　【Keywords】 collagen induced arthritis;rheumatoid arthritis;Hanbikang Tang（寒痹康汤）;Wnt/β-catenin;BMP/Smad;signal pathway;rats