本文關鍵詞： 類風濕關節(jié)炎 IL-6 JAK3 STAT3 痹祺膠囊　出處：《重慶醫(yī)科大學》2016年碩士論文　論文類型：學位論文

【摘要】：目的:探討細胞因子IL-6、JAK-STAT信號通路在類風濕關節(jié)炎(RA)的作用機制,觀察中成藥痹祺膠囊(BQC)對膠原誘導性(CIA)大鼠的作用及對細胞因子IL-6、JAK-STAT信號通路的影響,探討痹祺膠囊治療RA可能的作用機制。方法:以牛II型膠原(CII)和完全弗氏佐劑(CFA)制備CIA大鼠模型,隨機分為空白組、模型組、甲氨蝶呤組、BQC高中低劑量組進行給藥,每組12只大鼠。每周監(jiān)測各組大鼠足趾容積和體重變化。用藥12周后,ELISA法檢測大鼠血清中IL-6的水平;光鏡下觀察各組大鼠踝關節(jié)病理形態(tài)和JAK3、STAT3在大鼠關節(jié)踝軟骨和滑膜的表達;Western blot法檢測大鼠踝關節(jié)軟骨和滑膜中JAK3、STAT3蛋白表達水平;RT-PCR法檢測大鼠踝關節(jié)軟骨和滑膜中JAK3、STAT3的mRNA表達水平。結果:(1)模型組大鼠踝關節(jié)紅腫明顯,伴關節(jié)畸形、活動量減少及跛行;血清IL-6的水平明顯升高(P0.05);關節(jié)滑膜和軟骨中JAK3和STAT3的蛋白及mRNA的表達水平明顯升高(P0.05)。(2)各用藥組大鼠足趾腫脹度顯著減輕(P0.05),BQC高劑量組較其它用藥組減輕最明顯(P0.05)。(3)各用藥組大鼠血清IL-6的水平明顯降低,其中,BQC高中劑量組明顯優(yōu)于MTX組(P0.05);BQC低劑量組與MTX組作用相當(P0.05)。(4)各用藥組大鼠軟骨和滑膜中JAK3、STAT3蛋白及mRNA表達水平均明顯降低(P0.05),BQC高中劑量組優(yōu)于MTX組(P0.05),BQC低劑量組與MTX組相當(P0.05)。(5)光鏡下觀察空白組大鼠踝關節(jié)軟骨表面光滑,未見滑膜增生和血管翳生成。模型組大鼠踝關節(jié)滑膜大量增生、血管翳生成和軟骨破壞明顯。各用藥組大鼠滑膜增生和軟骨破壞明顯減輕,其中BQC高劑量組與MTX組作用相當,明顯優(yōu)于其他用藥組大鼠。結論:(1)CIA大鼠血清IL-6和關節(jié)軟骨和滑膜中JAK3、STAT3水平顯著升高,證明細胞因子IL-6、JAK3、STAT3在RA的發(fā)病機制和疾病進展中起著重要作用。(2)痹祺膠囊能明顯減輕CIA大鼠關節(jié)炎癥、滑膜增生、血管翳形成及關節(jié)軟骨和骨破壞,其機制可能與抑制炎癥因子IL-6、調控JAK-STAT信號通路中JAK3、STAT3的表達相關。
[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.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R259

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