發(fā)布時間：2018-04-04 12:22

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

【摘要】：目的：觀察中藥復方大黃散(CRP)外敷對類風濕關節(jié)炎(RA)大鼠的治療作用及對基質(zhì)金屬蛋白酶-10(MMP-10)、白細胞介素-33(IL-33)的影響,探討復方大黃散治療RA的療效與可能機制。方法：將72只SD大鼠隨機分成6組：正常組、模型組、扶他林組、甲氨蝶呤組、復方大黃散組、聯(lián)合組,除正常組外,用完全弗氏佐劑(CFA)復制誘導RA大鼠從模型,造模第8天,各用藥組分別給藥。以跖圍法測量大鼠足跖腫脹度；治療6周后,光鏡下觀察各組大鼠右踝關節(jié)病理學形態(tài)變化。Western Blotting檢測大鼠軟骨中MMP-10及IL-33的蛋自表達水平；RT-PCR法測定軟骨中IL-33.MMP-10的RNA表達水平。結(jié)果：模型組大鼠右后足關節(jié)紅腫明顯,伴活動量減少及跛行,軟骨中MMP-10及IL-33水平均明顯升高(P0.05),各用藥組關節(jié)腫脹明顯消退(P0.05),其中,聯(lián)合組大鼠關節(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及mRNA的表達含量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,模型組大鼠右踝關節(jié)組織中,大量炎性細胞出現(xiàn),并伴有漿細胞的浸潤,血管翳大量生成,關節(jié)腔間隙變窄,關節(jié)軟骨不同程度被破壞。各用藥組大鼠關節(jié)組織中血管翳生成減少,炎癥細胞浸潤減少,關節(jié)軟骨破壞減輕,關節(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大鼠踝關節(jié)中MMP-10、IL-33水平均明顯降低,二者呈正相關關系。證實RA的發(fā)病過程中可能通過MMP-10降解細胞外基質(zhì)(ECM)從而影響關節(jié)骨與軟骨的代謝,而1L-33通過介導Th2細胞免疫應答,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)復方大黃散能明顯減輕RA大鼠關節(jié)腫脹,并能改善RA關節(jié)軟骨與滑膜的病理學形態(tài),與口服甲氨蝶呤、外敷扶他林作用相當,其作用機制可能與通過抑制MMP-10、IL-33等細胞因子,從而達到早期控制RA滑膜炎發(fā)生,進而起到預防骨質(zhì)破壞等作用。以達到抗炎消腫、免疫調(diào)節(jié)、預防關節(jié)軟骨與骨破壞的作用。(3)復方大黃散外敷聯(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濕關節(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.
【學位授予單位】：重慶醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R593.22

【相似文獻】

相關期刊論文 前10條

1 陳同度,張昌穎;素食大鼠的貧血現(xiàn)象[J];營養(yǎng)學報;1957年04期

2 陳偉強;趙善廣;;自制注射用大鼠固定裝置[J];上海實驗動物科學;1992年04期

3 肖柳英,林培英,馮昭明,張丹;不同周齡的SD大鼠生理、生化及體重的正常值測定[J];中藥新藥與臨床藥理;1996年03期

4 李淑云;簡易大鼠灌胃器的制作[J];錦州醫(yī)學院學報;2001年04期

5 楊明智,陳積圣;一種大鼠抓取與固定的新工具介紹[J];上海實驗動物科學;2001年03期

6 戴英,陸群;復方H_(505)對Wistar大鼠外周血的血液流變學指標的影響[J];中國血液流變學雜志;2001年01期

7 韋應波,孫喜慶,曹新生,姚永杰,馮岱雅,楊長斌;+Gz暴露時間對大鼠記憶功能和行為的影響[J];航天醫(yī)學與醫(yī)學工程;2003年01期

8 呂學軍,郭俊生,李敏,周利梅,張永娟;暈船大鼠體內(nèi)鐵含量的變化[J];中國職業(yè)醫(yī)學;2003年04期

9 湯仁仙,王迎偉,王慧,周峰;201A中藥合劑對大鼠抗腎小球基底膜腎炎病變的影響[J];徐州醫(yī)學院學報;2003年06期

10 孫同柱,付小兵,翁立新,梁雪梅,陳偉;介紹一種簡易的大鼠保定方法[J];上海實驗動物科學;2004年01期

相關會議論文 前10條

1 尹音;孫振宇;胡敏;李冬霞;;持續(xù)性高正加速度對大鼠顳頜關節(jié)損傷的作用[A];第八屆全國顳下頜關節(jié)病學及（牙合）學大會論文匯編[C];2011年

2 祝~=驤;iJ梊霞;洃克琴;崔素英;文允摪;，

本文編號：1709934