机构地区:[1]重庆市中药研究院实验动物研究所,重庆400065 [2]第三军医大学全军免疫研究所,重庆400030 [3]重庆市中药研究院中药制剂所,重庆400065
出 处:《中药药理与临床》2017年第5期82-87,共6页Pharmacology and Clinics of Chinese Materia Medica
基 金:重庆市"集成示范"工程项目(cstc2013jcsf10011);重庆市社会民生科技创新专项:cstc2015shmszx10010资助
摘 要:目的:通过研究火把花根片对Lewis大鼠佐剂性关节炎模型关节肿胀度、血清中炎症因子浓度含量及调节性T细胞(Treg)比例等的影响,探讨火把花根片对佐剂性关节炎模型大鼠的治疗作用及可能的作用机制,为临床合理用药提供试验依据。方法:采用卡介苗联合弗氏不完全佐剂的方法诱导雄性Lewis大鼠建立佐剂性关节炎模型,观察不同给药剂量和不同给药时间对大鼠体重、左踝关节肿胀度及四肢关节指数的影响,酶联法测血清中IL-1α、IL-1β、TNF-α、IL-4、IL-10、MMP3浓度的变化,以及第21天时全血中Treg细胞比例变化和关节滑膜的病理变化。结果:火把花根片15g生药/kg和10g生药/kg剂量组踝关节肿胀度以及关节指数在治疗后7天、14天、21天均较模型组有明显下降;血清细胞因子IL-1α、IL-1β以及MMP3蛋白的浓度在治疗后14天、21天均较模型组有明显下降,IL-4、IL-10的浓度在治疗后14天、21天均较模型组有明显上升。给药后第21天,正常对照组以及火把花根片15g生药/kg和10g生药/kg剂量组的Treg细胞占T淋巴细胞比率较模型组明显为高;火把花根片15g生药/kg、10g生药/kg和5g生药/kg剂量组均能不同程度抑制足跖关节滑膜内炎性细胞浸润和巨噬细胞增生、抑制滑膜组织内滑膜与纤维组织增生。结论:火把花根片15g生药/kg和10g生药/kg连续给药3周均对大鼠佐剂性关节炎继发关节肿胀有明显的治疗作用,作用机制可能与其降低血清中促炎因子IL-1α、IL-1β及功能蛋白MMP3的浓度,升高血清中的抑炎因子IL-4、IL-10的浓度,增加调节性T细胞占T淋巴细胞的比例,抑制关节滑膜内炎细胞浸润与纤维增生有关。Objective: To discuss the therapeutic effect and the possible mechanism of Huobahua Root Tablets on adjuvant arthritis rats,by observing the swelling degree of rat adjuvant arthritis model,serum concentrations of inflammatory cytokines,and the proportion of regulatory T cells(Treg). Methods: The adjuvant arthritis model was induced in male Lewis rats by BCG combined with Freund's incomplete adjuvant. Effects of different dosages and the different administration time on body weight,the swelling degree of the left ankle and joint index were observed.Levels of L-1α,IL-1β,TNFα,IL-4,IL-10 and MMP3 in the serum of adjuvant arthritis rats were detected by enzyme-linked immunosorbent assay. The percentage of Treg cells in the whole blood and the morphological changes of synovial joint were observed on day 21. Results:Compared with the model group,the swelling degree of the ankle and arthritis index in huobahua root tablets treatment groups(10,15 g crude drug/kg) were significantly decreased on day 7,day 14,day21 after the administration.(P〈0. 05); concentrations of IL-1α,IL-1β and MMP3 in serum were decreased on day 14 and day 21 after the treatment(P〈0. 05),and concentrations of IL-4 and IL-10 were increased(P〈0. 05). Compared with the model group,the proportion of Treg cells in T lymphocytes in the control group and treatment groups(10、15 g crude drug/kg) were significantly increased on day 21 after treatment. 5、10、15 g crude drug/kg huobahua root tablets were able to inhibit the infiltration of inflammatory cells,the proliferation of macrophages,the proliferation of synovium and fibrous tissues in the synovial membrane. Conclusion: After 3 weeks of continuous administration,10,15 g crude drug/kg huobahua root tablets had obvious therapeutic effect on secondary swelling of adjuvant arthritis in rats. The mechanism may be related to the reduction of concentrations of proinflammatory factors IL-1α,IL-1β and MMP3 protein in serum,increase the production of anti-inflamma
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