{"title":"电针抑制慢性阻塞性肺疾病大鼠模型中的IL-17/IL-17R和后受体MAPK信号通路","authors":"Xin-Fang Zhang, Shui-Ying Xiang, Jing Lu, Yin Li, Shu-Jun Zhao, Chuan-Wei Jiang, Xiang-Guo Liu, Zi-Bing Liu, Jie Zhang","doi":"10.1177/0964528421996720","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":378725,"journal":{"name":"Acupuncture in medicine : journal of the British Medical Acupuncture Society","volume":" ","pages":"663-672"},"PeriodicalIF":0.0000,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/0964528421996720","citationCount":"11","resultStr":"{\"title\":\"Electroacupuncture inhibits IL-17/IL-17R and post-receptor MAPK signaling pathways in a rat model of chronic obstructive pulmonary disease.\",\"authors\":\"Xin-Fang Zhang, Shui-Ying Xiang, Jing Lu, Yin Li, Shu-Jun Zhao, Chuan-Wei Jiang, Xiang-Guo Liu, Zi-Bing Liu, Jie Zhang\",\"doi\":\"10.1177/0964528421996720\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":378725,\"journal\":{\"name\":\"Acupuncture in medicine : journal of the British Medical Acupuncture Society\",\"volume\":\" \",\"pages\":\"663-672\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1177/0964528421996720\",\"citationCount\":\"11\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acupuncture in medicine : journal of the British Medical Acupuncture Society\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1177/0964528421996720\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/3/15 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acupuncture in medicine : journal of the British Medical Acupuncture Society","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1177/0964528421996720","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/3/15 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 11
摘要
目的:白细胞介素(Interleukin, IL)-17是一种t -辅助性17细胞(Th17)细胞因子,在慢性阻塞性肺疾病(COPD)包括慢性炎症和气道阻塞等病理生理过程中起关键作用,导致肺功能下降。本研究旨在探讨针刺对慢性阻塞性肺疾病大鼠模型中IL-17及其受体(IL-17R)和丝裂原活化蛋白激酶(MAPK)信号通路的影响。方法:采用吸烟诱导大鼠慢性阻塞性肺病模型12周。采用电针(EA)治疗模型大鼠BL13和ST36。观察各组大鼠肺功能及组织学变化。采用酶联免疫吸附法(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、IL-10的含量。计数BALF中白细胞和巨噬细胞。采用实时聚合酶链反应(PCR)、western blotting和免疫组织化学检测肺组织中IL-17R的表达水平。通过western blotting在肺中观察到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:与对照组相比,COPD大鼠肺功能下降,肺实质出现严重炎症浸润。EA能有效改善COPD大鼠肺功能,减轻肺内炎症浸润。EA还逆转了COPD大鼠白细胞和巨噬细胞总数升高、IL-17和TNF-α水平升高以及IL-10含量降低。同时,EA下调了IL-17R mRNA和蛋白表达的升高,显著抑制了COPD大鼠肺中磷酸化JNK、ERK1/2、p38水平的升高。结论:针刺治疗对COPD大鼠肺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。
Electroacupuncture inhibits IL-17/IL-17R and post-receptor MAPK signaling pathways in a rat model of chronic obstructive pulmonary disease.
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.