益气活血解毒中药对胶原诱导性关节炎大鼠NF-κB信号通路相关因子表达的影响

Effects of Yiqi Huoxue Jiedu Fang on gene expression of cytokines involving NF-κB signal pathway in collagen Ⅱ-induced arthritic rats

目的探讨益气活血解毒中药对胶原诱导性关节炎(CIA)大鼠炎症细胞因子及NF-κB信号通路关键因子表达的影响。方法以牛Ⅱ型胶原尾根及背部多点注射制作CIA大鼠模型,以免疫抑制剂来氟米特为阳性对照药物,益气活血解毒中药干预,病理切片HE染色,观察大鼠足跖关节的病理改变,细胞因子芯片检测CIA大鼠血清中炎症细胞因子的含量,real-time PCR检测NF-κB信号通路中关键因子的基因表达改变。结果益气活血解毒中药可以明显抑制关节滑膜组织增生,缓解炎性渗出,缩小纤维素样坏死区范围,并显著降低CIA大鼠外周血血清中肿瘤坏死因子(TNF)α、白细胞介素(IL)-1β、IL-5、IL-6、IL-10的含量,NF-κB mRNA表达与模型组相比均显著下降(P<0.01或P<0.05),NF-k B抑制蛋白激酶mRNA表达有下降趋势,统计学分析差异无显著性。结论益气活血解毒中药可以通过干预与类风湿关节炎(RA)相关的炎症细胞因子和NF-κB信号通路相关因子的表达,抑制病变组织的炎症反应,修复炎症所导致的关节损伤,达到治疗RA的目的,这是益气活血解毒中药干预RA免疫炎症反应的关键作用机制之一。

Objective To study the gene expressions of key cytokines involving NF-κB signaling pathway in collagen II-induced arthritic （ CIA ） rats treated with Yiqi Huoxue Jiedu Fang （ qi-tonifying blood-activating and toxin-removing formula） .Methods We used collagen II-induced arthritic （ CIA） rats by bovine II collagen as an animal model and Leflunomide as controls.CIA rats received treatment with Yiqi Huoxue Jiedu Fang.The levels of inflammatory cytokines in serum were measured with protein chip assay, and hematoxylin dyeing was used to observe the histopathological changes.The gene expressions of the key cytokines in NF-κB signal pathway were detected by real-time PCR.Results This formula inhibited the proliferation of synovial tissues, reduced inflammatory exudation and narrowed the range of fibroid necrosis.It also down-regulated inflammatory cytokines （ TNF, IL-1, IL-5, IL-6 and IL-10） in serum of CIA rats.The gene expressions of NF-κB and IKK decreased in CIA rats treated with this formula.Conclusion Yiqi Huoxue Jiedu Fang could regulate the expressions of inflammatory cytokines and the key factor of NF-κB signal pathway for inhibiting inflammatory reaction in injured tissues, restoring the joint injury.Those could be the key active mechanism of RA treated with this formula.