乌骨藤对胶原诱导性关节炎大鼠IL-33/ST2信号通路的影响

Effect of Wugutengon on IL-33/ST2 signaling pathway in collagen-induced arthritis in rats

目的探讨乌骨藤对胶原诱导性关节炎(CIA)模型大鼠白细胞介素-33(IL-33)/生长刺激表达基因2蛋白(ST2)信号通路的影响。方法60只雌性Wistar大鼠随机分为空白组、模型组、来氟米特和乌骨藤低、中、高剂量组,后5组建立CIA大鼠模型;建模成功后,除空白组和模型组外,其余各组均予相应药物剂量灌胃4周,观察各组大鼠关节炎指数(AI);采用酶联免疫吸附法(ELISA)检测白细胞介素-4(IL-4)、白细胞介素-17A(IL-17A)、白细胞介素-33(IL-33)及γ干扰素(INF-γ)的水平;通过荧光定量PCR检测膝关节滑膜组织中促生长表达基因2(sST2)、跨膜型ST2(ST2L)、IL-33的mRNA表达;用蛋白质印迹(Western blot)检测大鼠滑膜组织中sST2、ST2L、IL-33蛋白表达。结果CIA大鼠成功建模,与模型组比较,来氟米特组、乌骨藤各剂量组大鼠血清中IL-17A、IL-33及INF-γ表达降低、L-4表达升高,膝关节滑膜组织sST2、ST2L、IL-33mRNA及蛋白表达降低,差异有统计学意义(P<0.05);与模型组比较,从治疗第3周开始,各给药组AI均有不同程度下降,差异有统计学意义(P<0.05)。结论乌骨藤可能通过调控IL-33/ST2信号相关蛋白和细胞因子的表达而发挥对CIA大鼠抗炎作用。

Objective To investigate the effect of Wuguteng on IL-33/ST2 signaling pathway in collagen-induced arthritis rats.Methods Sixty Wistar female rats were randomly divided into blank group,model group,leflunomide group,low-dose,medium-dose,and high-dose Wuguteng groups.After modeling,all groups were given corresponding drugs intragastric administration for 4 weeks except blank group and model group.The arthritis index(AI)of rats in each group were observed.The levels of IL-4,IL-17A,IL-33,and INF-γwere detected by ELISA.The mRNA expression of growth promoting expression gene(sST2),trans-synovial ST2L,and IL-33 in knee part synovial tissues of rats were detected by real-time PCR;Western blotting was adopted to detect protein expression of sST2,ST2L,and IL-33 in knee part synovial tissues of rats.Results CIA rats modeling was successful.Compared with model group,the expressions of IL-17A,IL-33,and INF-γin serum of leflunomide group and Wuguteng groups of all doses were decreased,the expressions of IL-4 were increased;the mRNA and protein expressions of sST2,ST2L,and IL-33 were decreased in knee part synovial tissues.The difference was statistically significant(P<0.05).Compared with model group,since the third week of treatment,arthritis indexes in all treatment groups decreased in different degrees,differences were statistically significant(P<0.05).Conclusion Wuguteng might play an anti-inflammatory role by regulating expression of related proteins and cytokines of IL-33/ST2 signal.