文献类型：期刊文献

中文题名：秦艽寒热不同配伍药对对风湿热痹类风湿关节炎大鼠MMP-3、TIMP-1表达及踝关节病理学改变的影响

英文题名：Effect of Gentianae Macrophyllae Radix in different combinations on expression of MMP-3,TIMP-1,and ankle pathological changes in wind-damp-heat arthralgia rheumatoid arthritis model rats

作者：马腾茂[1];刘飞[1];王蓉[1];孙少伯[1];高慧琴[1]

第一作者：马腾茂

机构：[1]甘肃中医药大学,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2017

卷号：48

期号：9

起止页码：1812

中文期刊名：中草药

外文期刊名：Chinese Traditional and Herbal Drugs

收录：CSTPCD;;Scopus;北大核心:【北大核心2014】；CSCD:【CSCD2017_2018】；

基金：国家自然科学基金资助项目(81360648)

语种：中文

中文关键词：秦艽;寒热药性;配伍;风湿热痹;类风湿关节炎;基质金属蛋白酶-3;金属蛋白酶组织抑制剂-1;威灵仙;桑寄生;防己

外文关键词：Gentianae Macrophyllae Radix; cold-heat nature; compatibility; rheumatic fever arthralgia; rheumatoid arthritis; MMP-3;TIMP- 1; Clematidis Radix et Rhizoma; Taxilli Herba; Stephanlae Tetrandrae Radix

摘要：目的研究秦艽寒热不同配伍药对对风湿热痹类风湿关节炎(RA)大鼠基质金属蛋白酶-3(MMP-3)和金属蛋白酶组织抑制剂-1(TIMP-1)表达的影响,并观察其踝关节病理学改变,探讨药性-病证-疗效之间的关系及中药治疗RA的机制。方法将80只健康SD大鼠随机分为对照组、Ⅱ型胶原(CⅡ)组、病证模型组、雷公藤多苷组、秦艽组、秦艽-威灵仙(秦-威)组、秦艽-桑寄生(秦-桑)组和秦艽-防己(秦-防)组8组,采用CⅡ诱导加风湿热环境因素刺激制备风湿热痹RA大鼠模型,各给药组ig给予制备的对应药液。实验中每3天测1次足跖厚度,计算足跖肿胀度;实验前期、中期、后期各进行1次关节炎指数(AI)评分。免疫组化法检测大鼠踝关节MMP-3和TIMP-1的表达,HE染色观察踝关节组织的病理学改变。结果与对照组比较,CⅡ组和病证模型组的足跖肿胀度、AI评分及MMP-3表达量均明显升高,TIMP-1表达量明显降低,CⅡ组和病证模型组大鼠关节面毛糙、破损,关节软骨破坏严重,大量肉芽组织增生,伴有大量的炎性细胞浸润和新生血管。经药物治疗后,与病证模型组比较,各给药组足跖肿胀度、AI和MMP-3表达量均有不同程度的降低,其中秦-防组降低最为显著;TIMP-1表达量均有不同程度的升高,其中秦-防组升高最为显著。HE染色结果显示,各给药组关节软骨破坏面积及破坏程度均有所减轻,炎性细胞及新生血管减少,修复纤维增多,瘢痕组织增多。结论对于风湿热痹RA,平寒相配效果优于平温、平平相配,实验结果与中医临床"疗热以寒药"的治疗原则是一致的,该配伍治疗风湿热痹RA的作用机制可能与其能够降低MMP-3表达、升高TIMP-1表达、减轻关节软骨破坏以及减少炎性细胞浸润和血管增生有关。
Objective To observe the effects ofGentianae Macrophyllae Radix （Qinjiao） in different combinations on the expression ofMMP-3, TIMP-1, and ankle pathologicat changes in rheumatoid arthritis （RA） model rats, and to explore the relationship between medicinal properties-disease-efficacy and explore the mechanism of traditional Chinese medicine in the treatment of RA. Methods Eighty SD rats were randomly divided into blank group, collage II model group, rheumatic fever model group, tripterygium group, single Qinjiao group, Qinjiao-Weilingxian （Clematidis Radix et Rhizoma） group, Qinjiao-Sangjisheng （Taxilli Herba） group, and Qinjiao-Fangji （Stephanlae Tetrandrae Radix） group. Rheumatic fever arthralgia model was induced by collage II and exposed in rheumatic fever environment. After modeling, each administration group was ig administrated with corresponding drug solution. The paw thickness was observed every 3 d, and swelling was calculated; The arthritis index was scored in the early, middle, and late stages. Rats were sacrificed on day 39. The expression of MMP-3 and TIMP-1 in the ankle joint of rats was detected by immunohistochemistry, and the pathological changes of ankle joint were observed by HE staining. Results Compared with the blank group, the paw edema, AI, and expression of MMP-3 in collage II model group and rheumatic fever model group was significantly higher, the expression of TIMP-1 were significantly lower, the articular surface of two groups was rough and damaged, and the articular cartilage was severely damaged. A large number of granulation tissues proliferated, accompanied by a large number of inflammatory cell infiltration and neovascularization. After treatment, compared with rheumatic fever model group, the paw edema, AI, and expression of MMP-3 in all treatment groups were reduced to varying degrees, in which the Qin-Fang group were lower most significant; The serum levels of TNF-α and IL-1β in all treatment groups were significantly decreased in varying degrees, especially in the Qin-Fang group; The expression of TIMP-1 was significantly increased in varying degrees, especially in the Qin-Fang group. HE staining results showed that the area of articular cartilage destruction and the degree of destruction were reduced, the inflammatory cells and neovascularization decreased, the number of repair fibers increased, and the scar tissue increased. Conclusion For the rheumatic fever arthralgia RA, the combined effect of mild and cold Chinese materia medica （CMM） is better than the combined effect of mild and warm CMM, the combined effect of mild CMMs. Experimental results are consistent with the principles of traditional Chinese medicine clinical treatment of ＂treating the hot diseases should use the Sold medicine＂, the mechanism of the compatibility drug relieving rheumatic fever arthralgia RA may be related to its ability, which can reduce the expression of MMP-3, increase the expression of TIMP-1, reduce articular cartilage destruction, and reduce inflammatory cell infiltration and vascular proliferation.