痹祺胶囊对CIA大鼠IL-6及JAK-STAT信号通路的影响

发布时间：2018-02-12 13:10

本文关键词： 类风湿关节炎 IL-6 JAK3 STAT3 痹祺胶囊　出处：《重庆医科大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的:探讨细胞因子IL-6、JAK-STAT信号通路在类风湿关节炎(RA)的作用机制,观察中成药痹祺胶囊(BQC)对胶原诱导性(CIA)大鼠的作用及对细胞因子IL-6、JAK-STAT信号通路的影响,探讨痹祺胶囊治疗RA可能的作用机制。方法:以牛II型胶原(CII)和完全弗氏佐剂(CFA)制备CIA大鼠模型,随机分为空白组、模型组、甲氨蝶呤组、BQC高中低剂量组进行给药,每组12只大鼠。每周监测各组大鼠足趾容积和体重变化。用药12周后,ELISA法检测大鼠血清中IL-6的水平;光镜下观察各组大鼠踝关节病理形态和JAK3、STAT3在大鼠关节踝软骨和滑膜的表达;Western blot法检测大鼠踝关节软骨和滑膜中JAK3、STAT3蛋白表达水平;RT-PCR法检测大鼠踝关节软骨和滑膜中JAK3、STAT3的mRNA表达水平。结果:(1)模型组大鼠踝关节红肿明显,伴关节畸形、活动量减少及跛行;血清IL-6的水平明显升高(P0.05);关节滑膜和软骨中JAK3和STAT3的蛋白及mRNA的表达水平明显升高(P0.05)。(2)各用药组大鼠足趾肿胀度显著减轻(P0.05),BQC高剂量组较其它用药组减轻最明显(P0.05)。(3)各用药组大鼠血清IL-6的水平明显降低,其中,BQC高中剂量组明显优于MTX组(P0.05);BQC低剂量组与MTX组作用相当(P0.05)。(4)各用药组大鼠软骨和滑膜中JAK3、STAT3蛋白及mRNA表达水平均明显降低(P0.05),BQC高中剂量组优于MTX组(P0.05),BQC低剂量组与MTX组相当(P0.05)。(5)光镜下观察空白组大鼠踝关节软骨表面光滑,未见滑膜增生和血管翳生成。模型组大鼠踝关节滑膜大量增生、血管翳生成和软骨破坏明显。各用药组大鼠滑膜增生和软骨破坏明显减轻,其中BQC高剂量组与MTX组作用相当,明显优于其他用药组大鼠。结论:(1)CIA大鼠血清IL-6和关节软骨和滑膜中JAK3、STAT3水平显著升高,证明细胞因子IL-6、JAK3、STAT3在RA的发病机制和疾病进展中起着重要作用。(2)痹祺胶囊能明显减轻CIA大鼠关节炎症、滑膜增生、血管翳形成及关节软骨和骨破坏,其机制可能与抑制炎症因子IL-6、调控JAK-STAT信号通路中JAK3、STAT3的表达相关。
[Abstract]:Objective: to investigate the mechanism of cytokine interleukin-6 (IL-6) JAK-STAT signaling pathway in rheumatoid arthritis (RA), and to observe the effect of BQCK on collagen-induced CIA-induced rat and cytokine IL-6 JAK-STAT signal pathway. To explore the possible mechanism of Biqi capsule in the treatment of RA. Methods: the CIA rat model was established with bovine type II collagen (CII) and complete Freund's adjuvant (CFAA). The rats were randomly divided into three groups: blank group, model group, methotrexate group, high and low dose group of BQC. The changes of toe volume and body weight of each group were monitored once a week. After 12 weeks of administration, the serum IL-6 levels were detected by Elisa. The pathological morphology of ankle joint and the expression of JAK3 / STAT3 in the articular cartilage and synovium of rats under light microscope the expression level of JAK3 / STAT3 protein in the articular cartilage and synovium of rats was detected by Western blot method. RT-PCR method was used to detect the expression of JAK3 / STAT3 protein in the cartilage and synovium of the rat ankle joint. The expression level of mRNA in JAK3 / STAT3. Results the swelling of ankle joint in the model group was obvious. Accompanied by deformities of joints, decreased activity and lameness; The level of serum IL-6 and the expression of JAK3 and STAT3 protein and mRNA in synovial membrane and cartilage were significantly increased. The level of serum IL-6 in the treatment group was significantly lower than that in the control group. The expression of JAK3STAT3 protein and mRNA in the cartilage and synovium of rats in the middle dose group was significantly lower than that in the low dose group of MTX group and that in the low dose group of MTX group and MTX group. The surface of ankle cartilage in blank group was smooth under light microscope. There was no synovial hyperplasia and pannus formation. The synovial membrane proliferation, pannus formation and cartilage damage were obvious in the model group. The synovial hyperplasia and cartilage damage were significantly alleviated in each medication group, and the effect of BQC high dose group was equal to that of MTX group. Conclusion the levels of serum IL-6 and JAK3-STAT3 in articular cartilage and synovium were significantly increased in rats treated with different drugs. It is demonstrated that IL-6, JAK3- STAT3 plays an important role in the pathogenesis and progression of RA.) Biqi capsule can significantly reduce arthritis, synovial hyperplasia, pannus formation and articular cartilage and bone destruction in CIA rats. The mechanism may be related to the inhibition of IL-6 and the regulation of JAK3-STAT3 expression in the JAK-STAT signaling pathway.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R259

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