基于Wnt/β-catenin信号通路探讨脊蛇祛湿胶囊治疗膝骨关节炎的作用机制  

Discussion on the mechanism of Jishe Qushi Capsule in treating knee osteoarthritis based on Wnt/β-catenin signaling pathway

作　　者：唐芳 蒋总 马武开 周静 兰维娅 蔡鑫 TANG Fang;JIANG Zong;MA Wu-kai;ZHOU Jing;LAN Wei-ya;CAI Xin(The Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550002,China)

机构地区：[1]贵州中医药大学第二附属医院,贵阳550002

出　　处：《中华中医药杂志》2023年第3期1032-1038,共7页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81760866,No.81760884);贵州省高层次创新型人才培养计划-“百”层次人才项目(N o.黔科合平台人才[2016]5650);国家重点研发计划中医药现代化研究重点专项(No.2017YFC1703904);贵州省中医药(民族医药)治疗风湿病医学平台建设(No.黔科合平台人才[2018]5707);贵州省中医风湿免疫疾病临床研究中心(No.黔科合平台人才[2020]2202号);贵州省教育厅青年科技人才成长项目(No.黔教合KY字[2022]262号)。

摘　　要：目的:探究脊蛇祛湿胶囊通过调控Wnt/β-catenin信号通路治疗膝骨关节炎(KOA)的作用机制。方法:70只大白兔随机分成7组:空白组,模型组,脊蛇祛湿胶囊低、中、高剂量组,盐酸氨基葡萄糖对照组及美洛昔康对照组,每组10只。造模、灌胃干预后,ELISA检测血清Wnt3a、Wnt5a、糖原合成酶激酶-3β(GSK-3β)、β-catenin、基质金属蛋白酶(MMP)13含量,HE染色观察膝关节软骨病理改变、AB-PAS染色进行Mankin’s评分,免疫组化检测软骨组织Wnt5a、Axin、GSK-3β、β-catenin、MMP13蛋白表达。结果:与空白组比较,模型组Mankin’s评分显著升高(P<0.05),血清中Wnt3a、Wnt5a、GSK-3β、β-catenin、MMP13含量显著升高(P<0.05),软骨组织中Wnt5a、GSK-3β、β-catenin、MMP13蛋白表达显著升高(P<0.05),Axin蛋白表达显著降低(P<0.05);与模型组比较,各药物组Mankin’s评分显著降低(P<0.05),血清中Wnt3a、Wnt5a、GSK-3β、β-catenin、MMP13含量均显著降低(P<0.05),软骨组织Wnt5a、GSK-3β、β-catenin、MMP13蛋白表达均显著降低(P<0.05),Axin蛋白显著升高(P<0.05);上述指标除MMP13含量外,脊蛇祛湿胶囊高剂量组改善均优于两个西药组(P<0.05)。结论:脊蛇祛湿胶囊可能通过抑制Wnt/β-catenin信号通路而发挥治疗KOA的作用。Objective:To explore the mechanism of Jishe Qushi Capsule in treating knee osteoarthritis(KOA)by regulating Wnt/β-catenin signaling pathway.Methods:Seventy white rabbits were randomly divided into 7 groups:blank group,model group,low,medium and high dose groups of Jishe Qushi Capsule,glucosamine hydrochloride control group and meloxicam control group,10 rabbits in each group.After modeling and gastric perfusion intervention,serum samples were taken to detect the contents of Wnt3a,Wnt5a,GSK-3β,β-catenin and MMP13.Knee cartilage samples were taken for HE staining to observe the pathological changes,AB-PAS staining for Mankin’s score,and the expressions of Wnt5a,Axin,GSK-3β,β-catenin and MMP13 were detected by immunohistochemistry.Results:Compared with the blank group,the Mankin’s score in the model group was significantly increased(P<0.05),the contents of Wnt3a,Wnt5a,GSK-3β,β-catenin and MMP13 in serum were significantly increased(P<0.05),Wnt5a,GSK-3β,β-catenin and MMP13 in cartilage tissue were significantly increased(P<0.05),and the expression of Axin protein decreased significantly(P<0.05).Compared with the model group,the Mankin’s score of each drug group decreased significantly(P<0.05),the contents of Wnt3a,Wnt5a,GSK-3β,β-catenin and MMP13 in serum decreased significantly(P<0.05),the expressions of Wnt5a,GSK-3β,β-catenin and MMP13 in cartilage tissue were significantly decreased(P<0.05),and the protein Axin was significantly increased(P<0.05).Except the content of MMP13,the improvement of the above indexes in the high-dose group of Jishe Qushi Capsule was better than that in the two western medicine groups(P<0.05).Conclusion:Jishe Qushi Capsule may play a role in treating KOA by inhibiting Wnt/β-catenin signaling pathway.

关 键 词：脊蛇祛湿胶囊 膝骨关节炎 软骨 AXIN WNT/Β-CATENIN信号通路 

分 类 号：R285.5[医药卫生—中药学]