乌头汤及四妙丸对人肿瘤坏死因子-α转基因关节炎小鼠模型的作用研究

Effects of Wutou Decoction and Simiao Pills on the human tumor necrosis factor-αtransgenic mice with rheumatoid arthritis

目的:探讨乌头汤、四妙丸对人肿瘤坏死因子-α转基因关节炎(Tgtc)小鼠模型的疗效,以反证法验证该小鼠模型的寒热属性,并探讨该模型的病理实质与缺氧诱导因子1α(HIF1α)及热休克蛋白70(HSP70)的关系。方法:32只Tgtc小鼠随机分为对照组、乌头汤组、四妙丸组和来氟米特组,每组8只。连续4周灌胃相应药物,记录各组踝关节变形指数、直径、颜色,进行双踝关节激光散斑血流成像,膝关节核磁共振扫描,血清及滑膜组织HIF1α、HSP70含量,踝关节组织病理及微血管密度(MVD)等检测。结果:与对照组比较,乌头汤组小鼠关节变形及红肿程度、关节表面散斑流速指数、膝关节积液面积、滑膜组织HIF1α含量及MVD计数均显著降低(P<0.05),血清及滑膜组织HSP70表达显著升高(P<0.05),关节病理中软骨层损伤深度及范围、炎症细胞浸润程度显著降低(P<0.01);四妙丸加重了Tgtc小鼠关节炎症状。结论:乌头汤通过改善关节缺氧,抑制HIF1α表达,并促进HSP70释放,减轻滑膜炎症及骨破坏,减缓Tgtc小鼠关节炎进展;Tgtc小鼠关节炎属性偏寒。

Objective:To compare the effect of Wutou Decoction(WTT)and Simiao Pills(SMW)on human tumor necrosis factor(TNF-α)transgenic(Tgtc)mice model of rheumatoid arthritis(RA),and to verify the cold and hot properties of Tgtc mice and to explore its mechanism.Methods:A total of 32 Tgtc mice were randomly divided into blank control(BC)group,leflunomide(LEF)group,WTT group and SMW group,8 in each group,the diameter of ankle joint,ankle joint deformation index and its color were recorded during administration.After four weeks administration,the laser speckle imaging was performed in two ankle joints,and magnetic resonance(MRI)was scanned in right knee;serum hyposia induced factor 1α(HIF1α)and heat shock protein-70(HSP70),ankle histopathological and immunohistochemical were also evaluated.Results:Compared with BC group,the degree of joint deformation,redness and swelling,speckled velocity index on joint surface,area of knee joint effusion,HIF1αcontent and MVD count in synovial tissue of mice in WTT group were significantly reduced(P<0.05),the expression of HSP70 in serum and synovial tissue was significantly increased(P<0.05),the depth and extent of cartilage layer injury and the degree of cell infiltration was significantly reduced(P<0.01);Simiao Pill aggravated the arthritis symptoms in Tgtc mice.Conclusion:Wutou Decoction can ameliorate joint hypoxia and inhibit expression of HIF1α,and promote the release of HSP70,reduce synovial inflammation and bone destruction,slow down the progression of arthritis in Tgtc mice;Tgtc mice have cold-bi syndrome properties.