A Novel Chinese Medicine, Xinfeng Capsule, Modulates Proinflammatory Cytokines via Regulating the Toll-Like Receptor 4 (TLR4)/Mitogen-Activated Protein Kinase (MAPK)/Nuclear Kappa B (NF-κB) Signaling Pathway in an Adjuvant Arthritis Rat Model
A Novel Chinese Medicine, Xinfeng Capsule, Modulates Proinflammatory Cytokines via Regulating the Toll-Like Receptor 4 (TLR4)/Mitogen-Activated Protein Kinase (MAPK)/Nuclear Kappa B (NF-κB) Signaling Pathway in an Adjuvant Arthritis Rat Model
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DOI：
10.12659/msm.916317
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发表时间：
2019-09-09
影响因子：
3.1
通讯作者：
Wang, Yuan
中科院分区：
文献类型：
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作者：
Cao, Yun-Xiang;Huang, Dan;Wang, Yuan
背景：类风湿性关节炎（RA）是一种以关节为靶点的慢性自身免疫性疾病。本研究旨在探讨新风胶囊（XFC）对佐剂性关节炎（AA）模型大鼠心脏损伤的影响及其机制。模型大鼠分为4组：AA模型组、黄芪多糖组、甲氨蝶呤组、消风胶囊加雷公藤组。苏木精-伊红（HE）染色观察组织病理学变化。TUNEL法检测心肌细胞凋亡。采用ELISA法检测心肌组织中肿瘤坏死因子α（TNF-α）、白细胞介素17（IL-17）和白细胞介素6（IL-6）的水平。采用定量RT-PCR（qRT-PCR）检测microRNA-21（miRNA 21）水平。结果：XFC能显著改善AA大鼠的促炎反应（p< 0.05）;与模型组相比，XFC治疗组TUNEL阳性细胞数显著减少（p< 0.05）。与模型组相比，XFC治疗显著降低心肌组织中TNF-α、IL-17和IL-6水平（p< 0.05）。与AA模型组相比，XFC组的miRNA 21水平显著降低（p< 0.05）。结论：新风胶囊通过调节TLR 4/MAPK/NF-κ B信号通路，对AA大鼠心肌损伤具有保护作用。
Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease targeting joints. This research aimed to explore the effects of Xinfeng capsules (XFC) on cardiac injury in adjuvant arthritis (AA) model rats and assessed the associated mechanism.Material/Methods: An adjuvant arthritis (AA) rat model was established by intracutaneously injection with Freund's complete adjuvant (FCA). Model rats were divided into 4 groups: an AA model group, an astragalus polysaccharides (APS) group, a methotrexate (MTX) group, and an XFC and triptolide (TPT) group. Hematoxylin-eosin (HE) staining was used to observe histopathologic changes. TUNEL assay was utilized to evaluate the apoptosis of cardiomyocytes. ELISA was utilized to evaluate levels of tumor necrosis factor a (TNF-alpha), interleukin 17 (IL-17), and interleukin 6 (IL-6) in myocardial tissues. Quantitative RT-PCR (qRT-PCR) was used to detect microRNA-21 (miRNA21) levels. Mitogen-activated protein kinase (MAPK)/p38, Toll-like receptor 4 (TLR4), and nuclear kappa B (NF-kappa B)/p65 levels were evaluated using Western blot.Results: XFC significantly improved proinflammatory response compared to the AA model group (p< 0.05). XFC treatment significantly decreased the number of cells staining TUNEL-positive compared with the model group (p< 0.05). XFC treatment significantly reduced TNF-alpha, IL-17, and IL-6 levels in myocardial tissues compared to the model group (p< 0.05). Levels of miRNA21 were significantly lower in the XFC group compared to the AA model group (p< 0.05). TLR4, MAPK/p38, and NF-kappa B/p65 expression levels were significantly lower in the XFC group than in the model group (p< 0.05).Conclusions: Xinfeng capsule, a traditional Chinese medicine preparation, protects against cardiac injury in AA rats by modulating proinflammatory cytokines expression via the TLR4/MAPK/NF-kappa B signaling pathway.