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电针对慢性阻塞性肺疾病大鼠模型中 IL-17/IL-17R 和受体后 MAPK 信号通路的抑制作用。

Electroacupuncture inhibits IL-17/IL-17R and post-receptor MAPK signaling pathways in a rat model of chronic obstructive pulmonary disease.

机构信息

Department of Physiology, College of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, China.

Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui University of Chinese Medicine, Hefei, China.

出版信息

Acupunct Med. 2021 Dec;39(6):663-672. doi: 10.1177/0964528421996720. Epub 2021 Mar 15.

Abstract

OBJECTIVE

Interleukin (IL)-17, as a T-helper 17 cell (Th17) cytokine, plays a key role in chronic obstructive pulmonary disease (COPD) pathophysiology including chronic inflammation and airway obstruction, which lead to decreased pulmonary function. The aim of this study was to investigate the effect of acupuncture on IL-17, its receptor (IL-17R) and the mitogen-activated protein kinase (MAPK) signaling pathway, in a rat model of COPD.

METHODS

The COPD model was induced in Sprague Dawley rats by exposure to cigarette smoke for 12 weeks. The model rats were treated with electroacupuncture (EA) at BL13 and ST36. The lung function and histology of the rats were observed. IL-17, tumor necrosis factor (TNF)-α, and IL-10 were detected by enzyme-linked immunosorbent assay (ELISA) in bronchoalveolar lavage fluid (BALF) and in plasma. The leukocytes and macrophages in the BALF were counted. The expression levels of IL-17R were assayed in lung tissue by real-time polymerase chain reaction (PCR), western blotting, and immunohistochemistry. MAPK signaling pathway molecules including c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK)1/2 and p38, and their phosphorylated forms, were observed in the lung by western blotting.

RESULTS

Compared with the control group rats, lung function decreased and there was a severe inflammatory infiltration of the pulmonary parenchyma in the COPD rats. EA effectively improved lung function and alleviated the inflammatory infiltration in the lungs of COPD rats. EA also reversed the elevated total leukocyte and macrophage counts, the high levels of IL-17 and TNF-α, and the low IL-10 content in COPD rats. Meanwhile, EA downregulated the increased mRNA and protein expression of IL-17R, and significantly inhibited the elevated levels of phosphorylated JNK, ERK1/2, and p38 in the lungs of COPD rats.

CONCLUSION

Our results suggest that the protective effects of acupuncture therapy on the lungs of COPD rats are likely related to inhibition of IL-17/IL-17R and the post-receptor MAPK signaling pathways.

摘要

目的

白细胞介素(IL)-17 作为辅助性 T 细胞 17 型(Th17)细胞因子,在慢性阻塞性肺疾病(COPD)的病理生理学中发挥关键作用,包括慢性炎症和气道阻塞,导致肺功能下降。本研究旨在探讨针刺对 COPD 大鼠模型中白细胞介素 17(IL-17)、其受体(IL-17R)和丝裂原活化蛋白激酶(MAPK)信号通路的影响。

方法

采用香烟烟雾暴露 12 周的方法诱导 Sprague Dawley 大鼠 COPD 模型。模型大鼠接受 BL13 和 ST36 电针(EA)治疗。观察大鼠肺功能和组织学变化。酶联免疫吸附试验(ELISA)检测支气管肺泡灌洗液(BALF)和血浆中 IL-17、肿瘤坏死因子(TNF)-α 和 IL-10 的水平。计数 BALF 中的白细胞和巨噬细胞。实时聚合酶链反应(PCR)、蛋白质印迹和免疫组织化学检测肺组织中 IL-17R 的表达水平。蛋白质印迹法观察肺组织中 MAPK 信号通路分子包括 c-Jun N-末端激酶(JNK)、细胞外信号调节激酶(ERK)1/2 和 p38 及其磷酸化形式。

结果

与对照组大鼠相比,COPD 大鼠肺功能下降,肺实质炎症浸润严重。EA 能有效改善 COPD 大鼠的肺功能,减轻肺部炎症浸润。EA 还逆转了 COPD 大鼠总白细胞和巨噬细胞计数升高、IL-17 和 TNF-α 水平升高、IL-10 含量降低。同时,EA 下调了 COPD 大鼠肺组织中 IL-17R 的 mRNA 和蛋白表达增加,并显著抑制了 COPD 大鼠肺组织中磷酸化 JNK、ERK1/2 和 p38 的升高水平。

结论

我们的研究结果表明,针刺疗法对 COPD 大鼠肺部的保护作用可能与抑制 IL-17/IL-17R 和受体后 MAPK 信号通路有关。

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