白芍总苷对类风湿性关节炎的治疗作用及Wnt/β-catenin通路的影响  

Therapeutic Effect of Total Glucosides of Paeony on Rheumatoid Arthritis and Its Influence on Wnt/β-catenin Pathway

作　　者：黄皆和 郑文标 管军辉[1] 杨晟[1] 王勇[1] 阮建伟[1] 王海宝[1] Huang Jiehe;Zheng Wenbiao;Guan Junhui;Yang Sheng;Wang Yong;Ruan Jianwei;Wang Haibao(Department of Orthopaedics,Taizhou Municipal Hospital,Zhejiang Taizhou 318000,China)

机构地区：[1]台州市立医院骨科,浙江台州318000

出　　处：《中国药师》2020年第2期218-223,共6页China Pharmacist

基　　金：浙江省中医药科学研究基金项目(编号:2018ZB136)。

摘　　要：目的:基于wingless/integrated(Wnt)/β-连环蛋白(β-catenin)信号转导通路研究白芍总苷治疗类风湿性关节炎的药效机制。方法:120只SD大鼠随机分成6组:正常对照组、模型组、地塞米松组(30.0 mg·kg^-1)、白芍总苷低、中、高剂量组(10.0,20.0,40.0 mg·kg^-1),每组20只。除正常对照组外,其余各组大鼠建立类风湿性关节炎模型,建模成功后地塞米松组、白芍总苷各剂量组给予相应药物灌胃,正常对照组和模型组给予等体积生理盐水。评估各组大鼠机械性痛阈(PWT)及热刺激缩足反射潜伏期(PWTL)、关节炎症积分水平,测定关节滑膜Wnt和β-catenin m RNA及蛋白水平以及白细胞介素2(IL-2)、白细胞介素6(IL-6)、肿瘤坏死因子(TNF-α)水平。结果:与正常对照组比较,模型组PWT、PWTL显著降低,关节炎症积分、Wnt和β-catenin m RNA及蛋白、IL-2、IL-6、TNF-α表达水平显著升高(P<0.05)。与模型组比较,地塞米松组和白芍总苷各剂量组PWT、PWTL显著升高,关节炎症积分、Wnt和β-catenin m RNA及蛋白、IL-2、IL-6、TNF-α表达水平显著降低(P<0.05),以上作用与白芍总苷剂量呈正相关(P<0.05)。其中白芍总苷低、中剂量组与地塞米松组比较差异有统计学意义(P<0.05)。正常对照组膝关节滑膜结构正常;模型组滑膜层增厚,大量中性粒细胞浸润;地塞米松组及白芍总苷高剂量组中性粒细胞浸润减少,滑膜明显变薄;白芍总苷低、中剂量组仍可见明显中性粒细胞浸润,滑膜局部粗糙不平。结论:白芍总苷可明显减少类风湿性关节炎引起的关节破坏,减轻类风湿性关节炎滑膜细胞损伤程度;其机制与白芍总苷可抑制Wnt和β-catenin m RNA及蛋白的表达进而抑制Wnt/β-catenin信号转导通路的激活有关。Objective:To investigate the pharmacodynamic mechanism of total glucosides of paeonia(TGP)in the treatment of rheumatoid arthritis based on Wnt/β-catenin signal transduction pathway.Methods:Totally 120 SD rats were randomly divided into six groups:the normal control group,the model group,dexamethasone group(30.0 mg·kg^-1),TGP low,medium and high dose groups(10.0,20.0 and 40.0 mg·kg^-1)with 20 rats in each group.Except the normal control group,the other groups of rats were used to establish rheumatoid arthritis model.After the successful establishment of the model,the corresponding drug was given intragastrically in dexamethasone group and TGP groups(1.0 ml/100 g)for 3 months.The normal control group and the model group were given normal saline with equal volume.After the experiment,the levels of PWT,PWTL and arthritis integral were evaluated,and the levels of Wnt andβ-catenin m RNA and protein,IL-2,IL-6 and TNF-αin synovium were measured.Results:Compared with those in the normal control group,PWT and PWTL significantly decreased,and the joint inflammation score,levels of Wnt andβ-catenin m RNA and protein,and expression levels of IL-2,IL-6 and TNF-αwere significantly increased in the model group(P<0.05).Compared with those in the model group,PWT and PWTL significantly increased,and the joint inflammation score,levels of Wnt andβ-catenin m RNA and protein,and expression levels of IL-2,IL-6 and TNF-αwere significantly decreased in dexamethasone group and all TGP groups(P<0.05).The above effects were positively correlated with the dose of TGP(P<0.05).There were significant differences between TGP low and middle dose groups and dexamethasone(P<0.05).The synovial structure of normal knee joints was normal;the synovial layer of the model group was thickened and a large number of neutrophils were infiltrated;the neutrophil infiltration was reduced in TGP high dose group and dexamethasone group,and the synovial membrane was thinner;TGP low and middle dose groups still showed obvious neutrophil infiltration,and t

关 键 词：Wnt/β-连环蛋白信号通路 白芍总苷 类风湿性关节炎 

分 类 号：R285.5[医药卫生—中药学]