青蒿素羟基氯喹复方对大鼠佐剂性关节炎的防治作用研究  

Study on the Preventive and Therapeutic Effect of Artemisinin-Hydroxychloroquine on Adjuvant Arthritis in Rats

作　　者：王兆佳 郑绍琴 刘敏 郭雪莹 陈颖谊 艾英 李国铭 员月明 张红英 宋健平 邓长生 WANG Zhaojia;ZHENG Shaoqin;LIU Min;GUO Xueying;CHEN Yingyi;AI Ying;LI Guoming;YUAN Yueming;ZHANG Hongying;SONG Jianping;DENG Changsheng(Artemisinin Research Center,Guangzhou University of Chinese Medicine,Guangzhou 510720 Guangdong,China;Institute of Science and Technology,Guangzhou University of Chinese Medicine,Guangzhou 510720 Guangdong,,China)

机构地区：[1]广州中医药大学青蒿研究中心,广东广州510720 [2]广州中医药大学科技产业园,广东广州510720

出　　处：《中药新药与临床药理》2022年第11期1487-1494,共8页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(81873218,82074301);广东省科技计划项目(2021A0505030060)。

摘　　要：目的 观察青蒿素羟基氯喹复方(AH)预防性给药对佐剂性关节炎(AA)大鼠的保护作用,探讨AH防治类风湿性关节炎的药效及机制。方法 在大鼠右后足跖皮内注射弗氏完全佐剂复制关节炎模型。致炎前1 d开始灌胃给药,连续给药至造模后30 d。收集致炎前后大鼠体质量、足肿胀度、关节炎指数等数据,观察预防性给药对大鼠原发性病变和继发性病变的影响;于实验终点采用ELISA法测定大鼠外周血中肿瘤坏死因子α(TNF-α)、干扰素γ(IFN-γ)、白细胞介素1β(IL-1β)、白细胞介素4(IL-4)含量;计算胸腺、脾脏及肾上腺指数;取大鼠踝关节行HE染色,对比组间组织病理学改变。结果 与正常对照组比较,模型对照组大鼠原发性足肿胀度(P<0.01)、关节炎指数(P<0.01)、血清中TNF-α和IL-1β含量(P<0.01)、踝关节病理形态结构评分总值(P<0.01)均明显升高。与模型对照组比较,AH各剂量组原发性足肿胀度在致炎后6、30、60、72 h明显下降(P<0.05,P<0.01),关节炎指数从第15天起明显下降(P<0.01);AH中、高剂量组佐剂性关节炎大鼠继发性足肿胀度下降程度从第15天开始明显下降(P<0.05,P<0.01),且从第24天起恢复至接近正常组水平(P>0.05)。AH各剂量均可明显减少大鼠血清中TNF-α和IL-1β的含量(P<0.01),其病理形态结构评分总值明显低于模型对照组(P<0.01)。结论 青蒿素羟基氯喹复方预防性给药对佐剂性关节炎大鼠的关节骨质破坏具有保护作用,其作用机制可能与减轻炎症反应、减少破骨细胞增生有关。Objective To observe the protective effect of prophylactic administration of artemisininhydroxychloroquine(AH)on adjuvant arthritis(AA)rats,and to explore the efficacy and mechanism of AH in the treatment of rheumatoid arthritis. Methods The arthritis model was established by intradermal injection of Freund’s complete adjuvant in the right hind paw of rats. Oral administration of drugs was started on day 1 before modeling and the same treatment continued for 30 days after modeling. The body weight,foot swelling,arthritis index before and after modeling were collected, and the effects of prophylactic administration on the primary and secondary lesions of the rats were observed. At the end of the experiment,tumor necrosis factor α(TNF-α),interferon γ(IFN-γ), interleukin 1β(IL-1β), and interleukin 4(IL-4) in peripheral blood were determined by ELISA.Thymus,spleen,and adrenal gland indexes were calculated. The ankle joints of rats were taken for HE staining,and histopathological changes between groups were compared. Results Compared with the normal control group,the primary foot swelling(P<0.01),the arthritis index(P<0.01),the contents of TNF-α and IL-1β in serum(P<0.01), and the total pathological score of ankle joint(P<0.01) in the model control group were significantly increased. Compared with the model control group,the primary foot swelling in each dose group of AH decreased significantly at 6,30,60,72 hours after inflammation(P<0.05,P<0.01),and the arthritis index decreased significantly on the 15th day after inflammation(P<0.01). The secondary foot swelling of AA rats in AH middleand high-dose groups decreased significantly on the 15th day after inflammation(P<0.05, P<0.01), and recovered to the level close to the normal group from the 24th day(P>0.05). Each dose of AH could significantly reduce the levels of TNF-α and IL-1β in the serum of rats(P<0.01), and the total pathological score was significantly lower than that of the model control group(P<0.01). Conclusion The prophylactic administration

关 键 词：青蒿素 羟基氯喹 类风湿性关节炎 佐剂性关节炎 预防性给药 炎性细胞因子 破骨细胞 大鼠 

分 类 号：R285.5[医药卫生—中药学]