本文選題：類風(fēng)濕關(guān)節(jié)炎　切入點(diǎn)：基質(zhì)金屬蛋白酶-10　出處：《重慶醫(yī)科大學(xué)》2015年碩士論文

【摘要】：目的：觀察中藥復(fù)方大黃散(CRP)外敷對(duì)類風(fēng)濕關(guān)節(jié)炎(RA)大鼠的治療作用及對(duì)基質(zhì)金屬蛋白酶-10(MMP-10)、白細(xì)胞介素-33(IL-33)的影響,探討復(fù)方大黃散治療RA的療效與可能機(jī)制。方法：將72只SD大鼠隨機(jī)分成6組：正常組、模型組、扶他林組、甲氨蝶呤組、復(fù)方大黃散組、聯(lián)合組,除正常組外,用完全弗氏佐劑(CFA)復(fù)制誘導(dǎo)RA大鼠從模型,造模第8天,各用藥組分別給藥。以跖圍法測(cè)量大鼠足跖腫脹度；治療6周后,光鏡下觀察各組大鼠右踝關(guān)節(jié)病理學(xué)形態(tài)變化。Western Blotting檢測(cè)大鼠軟骨中MMP-10及IL-33的蛋自表達(dá)水平；RT-PCR法測(cè)定軟骨中IL-33.MMP-10的RNA表達(dá)水平。結(jié)果：模型組大鼠右后足關(guān)節(jié)紅腫明顯,伴活動(dòng)量減少及跛行,軟骨中MMP-10及IL-33水平均明顯升高(P0.05),各用藥組關(guān)節(jié)腫脹明顯消退(P0.05),其中,聯(lián)合組大鼠關(guān)節(jié)腫脹消退最明顯(P0.05),其余三組之間無明顯差異(P0.05)。治療6周后,與模型組比較,各用藥組軟骨蛋白表達(dá)及mRNA的表達(dá)含量MMP-10、IL-33水平均顯著下降(P0.05),其中,聯(lián)合組下降更明顯(P0.05)。光鏡下觀察,模型組大鼠右踝關(guān)節(jié)組織中,大量炎性細(xì)胞出現(xiàn),并伴有漿細(xì)胞的浸潤(rùn),血管翳大量生成,關(guān)節(jié)腔間隙變窄,關(guān)節(jié)軟骨不同程度被破壞。各用藥組大鼠關(guān)節(jié)組織中血管翳生成減少,炎癥細(xì)胞浸潤(rùn)減少,關(guān)節(jié)軟骨破壞減輕,關(guān)節(jié)腔間隙狹窄明顯改善。以聯(lián)合組改善更明顯。結(jié)論：(1)RA大鼠踝關(guān)節(jié)中MMP-10、IL-33水平均明顯降低,二者呈正相關(guān)關(guān)系。證實(shí)RA的發(fā)病過程中可能通過MMP-10降解細(xì)胞外基質(zhì)(ECM)從而影響關(guān)節(jié)骨與軟骨的代謝,而1L-33通過介導(dǎo)Th2細(xì)胞免疫應(yīng)答,破壞Thl/Th2平衡,在RA的發(fā)生發(fā)展中也起到了重要的致炎癥作用。(2)復(fù)方大黃散能明顯減輕RA大鼠關(guān)節(jié)腫脹,并能改善RA關(guān)節(jié)軟骨與滑膜的病理學(xué)形態(tài),與口服甲氨蝶呤、外敷扶他林作用相當(dāng),其作用機(jī)制可能與通過抑制MMP-10、IL-33等細(xì)胞因子,從而達(dá)到早期控制RA滑膜炎發(fā)生,進(jìn)而起到預(yù)防骨質(zhì)破壞等作用。以達(dá)到抗炎消腫、免疫調(diào)節(jié)、預(yù)防關(guān)節(jié)軟骨與骨破壞的作用。(3)復(fù)方大黃散外敷聯(lián)合甲氨蝶呤組治療緩解RA大鼠足腫脹的療效更佳,調(diào)控MMP-10、IL-33等細(xì)胞因子作用更明顯,說明中藥外敷聯(lián)合甲氨蝶呤是一種有效的治療類風(fēng)濕關(guān)節(jié)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.
【學(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2015
【分類號(hào)】：R593.22

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