PM10 暴露通过上调乙酰胆碱毒蕈碱 3 受体诱导支气管高反应性。

IF 3.3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Xue Xiao , Yali Lei , Tong Yao , Tingting Huang , Pingping Yan , Lei Cao , Yongxiao Cao
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引用次数: 0

摘要

暴露于颗粒物(PM10)可诱发呼吸系统疾病,这些疾病与支气管高反应性密切相关。然而,其中的机制仍有待全面阐明。本研究旨在证明 PM10 对大鼠支气管平滑肌乙酰胆碱毒蕈碱 3 受体(CHRM3)表达的影响以及 ERK1/2 通路的作用。采用全身 PM10 暴露系统刺激大鼠支气管高反应性 2 个月和 4 个月,同时注射 MEK1/2 抑制剂 U0126。全身胸透系统和肌电图分别用于检测肺功能和支气管收缩功能。通过 Western 印迹、qPCR 和免疫荧光测定 mRNA 和蛋白质水平。酶联免疫吸附试验用于检测炎症细胞因子。与过滤空气组相比,暴露 4 个月的 PM10 会显著增加 CHRM3 介导的肺功能和支气管收缩,升高支气管平滑肌上 CHRM3 mRNA 和蛋白表达水平,进而诱导支气管高反应性。此外,暴露于 PM10 4 个月会导致 ERK1/2 磷酸化增加,并增加支气管肺泡灌洗液中炎性因子的分泌。用 MEK1/2 抑制剂 U0126 治疗可抑制 PM10 暴露诱导的 ERK1/2 通路磷酸化,从而减少 PM10 暴露诱导的支气管平滑肌中 CHRM3 的上调和 CHRM3 介导的支气管收缩。U0126 可以挽救 PM10 暴露诱导的支气管病理变化。总之,PM10 暴露可通过上调 CHRM3 诱导大鼠支气管高反应性,而 ERK1/2 通路可能参与了这一过程。这些发现可能为空气污染诱发的呼吸系统疾病提供了潜在的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

PM10 exposure induces bronchial hyperresponsiveness by upreguating acetylcholine muscarinic 3 receptor

PM10 exposure induces bronchial hyperresponsiveness by upreguating acetylcholine muscarinic 3 receptor

Exposure to particulate matter (PM10) can induce respiratory diseases that are closely related to bronchial hyperresponsiveness. However, the involved mechanism remains to be fully elucidated. This study aimed to demonstrate the effects of PM10 on the acetylcholine muscarinic 3 receptor (CHRM3) expression and the role of the ERK1/2 pathway in rat bronchial smooth muscle. A whole-body PM10 exposure system was used to stimulate bronchial hyperresponsiveness in rats for 2 and 4 months, accompanied by MEK1/2 inhibitor U0126 injection. The whole-body plethysmography system and myography were used to detect the pulmonary and bronchoconstrictor function, respectively. The mRNA and protein levels were determined by Western blotting, qPCR, and immunofluorescence. Enzyme-linked immunosorbent assay was used to detect the inflammatory cytokines. Compared with the filtered air group, 4 months of PM10 exposure significantly increased CHRM3-mediated pulmonary function and bronchial constriction, elevated CHRM3 mRNA and protein expression levels on bronchial smooth muscle, then induced bronchial hyperreactivity. Additionally, 4 months of PM10 exposure caused an increase in ERK1/2 phosphorylation and increased the secretion of inflammatory factors in bronchoalveolar lavage fluid. Treatment with the MEK1/2 inhibitor, U0126 inhibited the PM10 exposure-induced phosphorylation of the ERK1/2 pathway, thereby reducing the PM10 exposure-induced upregulation of CHRM3 in bronchial smooth muscle and CHRM3-mediated bronchoconstriction. U0126 could rescue PM10 exposure-induced pathological changes in the bronchus. In conclusion, PM10 exposure can induce bronchial hyperresponsiveness in rats by upregulating CHRM3, and the ERK1/2 pathway may be involved in this process. These findings could reveal a potential therapeutic target for air pollution induced respiratory diseases.

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来源期刊
CiteScore
6.80
自引率
2.60%
发文量
309
审稿时长
32 days
期刊介绍: Toxicology and Applied Pharmacology publishes original scientific research of relevance to animals or humans pertaining to the action of chemicals, drugs, or chemically-defined natural products. Regular articles address mechanistic approaches to physiological, pharmacologic, biochemical, cellular, or molecular understanding of toxicologic/pathologic lesions and to methods used to describe these responses. Safety Science articles address outstanding state-of-the-art preclinical and human translational characterization of drug and chemical safety employing cutting-edge science. Highly significant Regulatory Safety Science articles will also be considered in this category. Papers concerned with alternatives to the use of experimental animals are encouraged. Short articles report on high impact studies of broad interest to readers of TAAP that would benefit from rapid publication. These articles should contain no more than a combined total of four figures and tables. Authors should include in their cover letter the justification for consideration of their manuscript as a short article.
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