复方大黄散外敷对类风湿关节炎大鼠MMP-10、IL-33的影响

发布时间：2018-04-04 12:22

本文选题：类风湿关节炎　切入点：基质金属蛋白酶-10　出处：《重庆医科大学》2015年硕士论文

【摘要】：目的：观察中药复方大黄散(CRP)外敷对类风湿关节炎(RA)大鼠的治疗作用及对基质金属蛋白酶-10(MMP-10)、白细胞介素-33(IL-33)的影响,探讨复方大黄散治疗RA的疗效与可能机制。方法：将72只SD大鼠随机分成6组：正常组、模型组、扶他林组、甲氨蝶呤组、复方大黄散组、联合组,除正常组外,用完全弗氏佐剂(CFA)复制诱导RA大鼠从模型,造模第8天,各用药组分别给药。以跖围法测量大鼠足跖肿胀度；治疗6周后,光镜下观察各组大鼠右踝关节病理学形态变化。Western Blotting检测大鼠软骨中MMP-10及IL-33的蛋自表达水平；RT-PCR法测定软骨中IL-33.MMP-10的RNA表达水平。结果：模型组大鼠右后足关节红肿明显,伴活动量减少及跛行,软骨中MMP-10及IL-33水平均明显升高(P0.05),各用药组关节肿胀明显消退(P0.05),其中,联合组大鼠关节肿胀消退最明显(P0.05),其余三组之间无明显差异(P0.05)。治疗6周后,与模型组比较,各用药组软骨蛋白表达及mRNA的表达含量MMP-10、IL-33水平均显著下降(P0.05),其中,联合组下降更明显(P0.05)。光镜下观察,模型组大鼠右踝关节组织中,大量炎性细胞出现,并伴有浆细胞的浸润,血管翳大量生成,关节腔间隙变窄,关节软骨不同程度被破坏。各用药组大鼠关节组织中血管翳生成减少,炎症细胞浸润减少,关节软骨破坏减轻,关节腔间隙狭窄明显改善。以联合组改善更明显。结论：(1)RA大鼠踝关节中MMP-10、IL-33水平均明显降低,二者呈正相关关系。证实RA的发病过程中可能通过MMP-10降解细胞外基质(ECM)从而影响关节骨与软骨的代谢,而1L-33通过介导Th2细胞免疫应答,破坏Thl/Th2平衡,在RA的发生发展中也起到了重要的致炎症作用。(2)复方大黄散能明显减轻RA大鼠关节肿胀,并能改善RA关节软骨与滑膜的病理学形态,与口服甲氨蝶呤、外敷扶他林作用相当,其作用机制可能与通过抑制MMP-10、IL-33等细胞因子,从而达到早期控制RA滑膜炎发生,进而起到预防骨质破坏等作用。以达到抗炎消肿、免疫调节、预防关节软骨与骨破坏的作用。(3)复方大黄散外敷联合甲氨蝶呤组治疗缓解RA大鼠足肿胀的疗效更佳,调控MMP-10、IL-33等细胞因子作用更明显,说明中药外敷联合甲氨蝶呤是一种有效的治疗类风湿关节炎的方法。
[Abstract]:Objective: to observe the therapeutic effect of traditional Chinese medicine compound rhubarb powder (CRP) on rheumatoid arthritis (RA) rats and its effect on matrix metalloproteinase-10 (MMP-10) and interleukin-33 (IL-33), and to explore the therapeutic effect and possible mechanism of compound rhubarb powder in the treatment of RA.Methods: 72 SD rats were randomly divided into 6 groups: normal group, model group, Futalin group, methotrexate group, compound rhubarb powder group, combined group.Each medication group was given respectively.After 6 weeks of treatment, the pathological changes of right ankle joint in each group were observed under light microscope. Western Blotting was used to detect the egg self-expression level of MMP-10 and IL-33 in the cartilage of rats. RT-PCR was used to detect the expression of IL-33.MMP-10 in the cartilage.Results: in the model group, the swelling of the right hind foot joint was obvious, the amount of movement was decreased and claudication. The levels of MMP-10 and IL-33 in the cartilage were significantly increased (P 0.05), and the swelling of the joints in each medication group disappeared obviously (P 0.05).The joint swelling in the combined group was the most obvious (P 0.05), but there was no significant difference among the other three groups.After 6 weeks of treatment, compared with the model group, the expression of chondroprotein and the expression of MMP-10, IL-33 in each drug group were significantly lower than those in the model group, among which, the decrease in the combined group was more obvious than that in the combined group.Under the light microscope, a large number of inflammatory cells appeared in the right ankle joint of the model group, accompanied by the infiltration of plasma cells, the formation of pannus, the narrowing of articular space and the destruction of articular cartilage to varying degrees.The formation of pannus, the infiltration of inflammatory cells, the destruction of articular cartilage and the stenosis of articular space were decreased in each group.The improvement was more obvious in the combined group.Conclusion the levels of MMP-10 and IL-33 in the ankle joint of the rats were significantly lower than those of the control group, and there was a positive correlation between them.It is suggested that the pathogenesis of RA may affect the metabolism of articular bone and cartilage through the degradation of extracellular matrix (ECM) by MMP-10, while 1L-33 may disrupt the balance of Thl/Th2 by mediating the immune response of Th2 cells.Compound rhubarb powder can obviously reduce the joint swelling and improve the pathological morphology of articular cartilage and synovium of RA rats, which is similar to that of oral methotrexate and external application of Fentalin.The mechanism may be related to the inhibition of MMP-10, IL-33 and other cytokines, so as to control the occurrence of RA synovitis at an early stage and thus prevent the destruction of bone.The effect of compound rhubarb powder combined with methotrexate group on relieving foot swelling in RA rats was better, and the effect of regulating cytokines such as MMP-10, IL-33 and other cytokines was more obvious, in order to achieve anti-inflammatory, anti-swelling, immunomodulation and prevention of articular cartilage and bone damage, the effect of compound rhubarb powder combined with methotrexate group was better.It shows that the combination of Chinese medicine and methotrexate is an effective treatment for rheumatoid arthritis.
【学位授予单位】：重庆医科大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R593.22

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