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作 者:刘方圆 朱继孝 刘琳 孙杰 王钰洁 杨静 曾金祥 李敏 LIU Fang-yuan;ZHU Ji-xiao;LIU Lin;SUN Jie;WANG Yu-jie;YANG Jing;ZENG Jin-xiang;LI Min(Jiangxi University of Traditional Chinese Medicine,Research Center of Chinese Herbal Medicine and Ethnic Medicine,Nanchang 330004,China;Shandong Jincheng Pharmaceutical Group Co.,Ltd.,Zibo Shandong 255000,China)
机构地区:[1]江西中医药大学,中药资源与民族药研究中心,江西南昌330004 [2]山东金城医药集团股份有限公司,山东淄博255000
出 处:《中国药理学通报》2023年第7期1378-1384,共7页Chinese Pharmacological Bulletin
基 金:国家重点研发计划项目(No.2019YFC1712300)。
摘 要:目的明确藏药臭蚤草抗类风湿性关节炎的作用,筛选其抗类风湿性关节炎的活性部位,初步探讨其抗类风湿性关节炎作用机制。方法以牛Ⅱ型胶原与弗氏不完全佐剂建立大鼠类风湿性关节炎(CIA)模型。观察臭蚤草总提物、大孔树脂不同浓度乙醇洗脱部位及雷公藤多苷(GTW)对类风湿性关节炎模型大鼠的足肿胀度的影响,检测大鼠血清中的肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)和类风湿性因子(RF)的含量,借助滑膜组织病理学验证臭蚤草对类风湿性关节炎的治疗作用,利用Western blot法探究臭蚤草对类风湿性关节炎大鼠滑膜组织中MAPK/p38/NF-κB、TLR4/NF-κB炎症通路蛋白表达的影响,探讨臭蚤草抗类风湿性关节炎的作用机制。结果与模型组相比,臭蚤草总提取物和大孔树脂60%乙醇洗脱部位能够明显降低CIA大鼠关节肿胀度;有效改善大鼠滑膜的病理变化,并明显降低血清中炎症因子中大鼠肿瘤坏死因子(TNF-α)、白细胞介素-1β(IL-1β)和类风湿性因子(RF)水平;明显降低滑膜组织中(TLR4、NF-κB、Myd88、p-p38、p-IκBα、iNOS等)相关炎症蛋白的表达。结论(1)臭蚤草可以缓解类风湿性关节炎大鼠的关节炎症症状,且臭蚤草60%乙醇洗脱部位为臭蚤草抗类风湿性关节炎的有效活性部位;(2)臭蚤草总提物及不同极性提取物能抑制MAPK/p38/NF-κB、TLR4/NF-κB信号通路缓解CIA大鼠的关节炎症状。Aim To clarify the anti-rheumatoid arthritis effect of Tibetan medicine Pulicaria insignis(P.insignis),sift out the active parts against rheumatoid arthritis,and investigate the mechanism.Methods Rat rheumatoid arthritis(CIA)model was established with bovine typeⅡcollagen and incomplete Freund′s adjuvant.The effects of the total extract of P.insignis,macroporous resin eluted parts with different concentrations of ethanol and Tripterygium Glycosides(GTW)on the degree of foot swelling in CIA rats were observed,the levels of tumor necrosis factor(TNF-α),intd rheumaerleukin-1β(IL-1β)antoid factor(RF)in serum of rats were detected,the pathological changes of synovial tissues were investigated,and the effects on MAPK/p38/NF-κB,TLR4/NF-κB protein expressions were explored by Western blot.Results Compared with the model group,the total extract of P.insignis and the eluted part of macroporous resin 60%ethanol could significantly reduce the degree of joint swelling in CIA rats,effectively improve the pathological changes of rats synovium tissues,and significantly reduce the levels of rat tumor necrosis factor(TNF-α),interleukin-1β(IL-1β)and rheumatoid factor(RF)in serum inflammatory factors,and markedly decrease the expression of related inflammatory proteins(TLR4,NF-κB,Myd88,p-p38,p-IκBα,iNOS,etc)in synovial tissue.Conclusions(1)P.insignis can relieve the symptoms of joint inflammation in rats with rheumatoid arthritis,and the eluted part of macroporous resin 60%ethanol of P.insignis is the effective active part for anti-rheumatoid arthritis.(2)The total and partial extracts of P.insignis can relieve arthritis symptoms in CIA rats through inhibiting the MAPK/p38/NF-κB and TLR4/NF-κB signaling pathways.
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