二苗散通过miRNA-33/NLRP3信号通路对佐剂性关节炎大鼠腹腔巨噬细胞极化的影响

IF 3.9 3区 医学 Q1 MEDICAL LABORATORY TECHNOLOGY
Min Liu, Xiangwen Meng, Zihua Xuan, Simeng Chen, Jin Wang, Zhiluo Chen, Jiayu Wang, Xiaoyi Jia
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引用次数: 10

摘要

背景:二苗散(EMS)是由苍术与黄柏按1:1比例配制而成,常用于治疗类风湿性关节炎(RA)等炎性疾病。目的:探讨EMS对大鼠佐剂性关节炎(AA)模型腹腔巨噬细胞分化的作用机制及影响。材料和方法:EMS(3、1.5、0.75 g/kg;每日一次)和甲氨蝶呤(0.5 mg/kg;免疫后第21 ~ 35天口服(每3天1次)。测量足跖肿胀和关节炎指数;x线及苏木精伊红染色观察踝关节病理改变。流式细胞术检测巨噬细胞中CD86/CD206的比值。RT-qPCR和western blotting检测miRNA-33/NLRP3信号通路。ELISA法检测血清和细胞上清液中细胞因子水平。结果:EMS显著降低大鼠AA指数(由11.0降至9.3)和踝关节病理改变(由3.8降至1.4)。ems处理大鼠巨噬细胞中CD86/CD206的比值降低,对M1的极化从0.9提高到0.6。EMS下调miRNA-33/NLRP3通路。EMS处理提高了AA大鼠巨噬细胞血清和上清液中IL-10和TGF-β水平,同时降低了IL-1β和TNF-α水平。讨论和结论:我们的研究结果表明,EMS可能通过下调AA大鼠的miRNA-33/NLRP3通路,使巨噬细胞极化到M1炎症表型。这些发现可能为类风湿关节炎的治疗提供新的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Effect of Er Miao San on peritoneal macrophage polarisation through the miRNA-33/NLRP3 signalling pathway in a rat model of adjuvant arthritis.

Effect of Er Miao San on peritoneal macrophage polarisation through the miRNA-33/NLRP3 signalling pathway in a rat model of adjuvant arthritis.

Effect of Er Miao San on peritoneal macrophage polarisation through the miRNA-33/NLRP3 signalling pathway in a rat model of adjuvant arthritis.

Effect of Er Miao San on peritoneal macrophage polarisation through the miRNA-33/NLRP3 signalling pathway in a rat model of adjuvant arthritis.

Context: Er Miao San (EMS) is a formulation that contains Atractylodis Rhizoma and Phellodendri Cortex in 1:1 ratio, and is commonly used to treat rheumatoid arthritis (RA) and other inflammatory diseases.

Objective: We investigated the mechanism of action and effects of EMS on peritoneal macrophage differentiation in a rat model of adjuvant arthritis (AA).

Materials and methods: EMS (3, 1.5 and 0.75 g/kg; once daily) and methotrexate (0.5 mg/kg; once every 3 days) were administered orally from days 21 to 35 after immunisation. Paw swelling and arthritis index were measured; pathological changes in the ankle joint were observed using x-ray and haematoxylin eosin staining. The ratio of CD86/CD206 in macrophages was detected by flow cytometry. Examination of the miRNA-33/NLRP3 signalling pathway was examined by RT-qPCR and western blotting. The levels of cytokines in the serum and cell supernatants were tested by ELISA.

Results: EMS significantly reduced the AA index in rats (from 11.0 to 9.3) and pathological changes in the ankle joint (from 3.8 to 1.4). The ratio of CD86/CD206 was reduced, and polarisation to M1 improved (from 0.9 to 0.6) in macrophages of EMS-treated rats. EMS downregulated the miRNA-33/NLRP3 pathway. Furthermore, EMS treatment increased IL-10 and TGF-β levels in the serum and supernatant of macrophages of AA rats and simultaneously decreased the levels of IL-1β and TNF-α.

Discussion and conclusions: Our results suggest that EMS may reduce macrophage polarisation to the M1 inflammatory phenotype by downregulating the miRNA-33/NLRP3 pathway in AA rats. These findings may provide new insights into the treatment of RA.

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来源期刊
Pharmaceutical Biology
Pharmaceutical Biology 医学-药学
CiteScore
6.70
自引率
2.60%
发文量
191
审稿时长
1 months
期刊介绍: Pharmaceutical Biology will publish manuscripts describing the discovery, methods for discovery, description, analysis characterization, and production/isolation (including sources and surveys) of biologically-active chemicals or other substances, drugs, pharmaceutical products, or preparations utilized in systems of traditional medicine. Topics may generally encompass any facet of natural product research related to pharmaceutical biology. Papers dealing with agents or topics related to natural product drugs are also appropriate (e.g., semi-synthetic derivatives). Manuscripts will be published as reviews, perspectives, regular research articles, and short communications. The primary criteria for acceptance and publication are scientific rigor and potential to advance the field.
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