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PM2.5对卵清蛋白致敏和激发小鼠的加剧作用及肺组织中TRPA1和TRPV1蛋白的表达

Exacerbating effects of PM2.5 in OVA-sensitized and challenged mice and the expression of TRPA1 and TRPV1 proteins in lungs.

作者信息

Liu Hong, Fan Xinsheng, Wang Naiqian, Zhang Yuyan, Yu Jinghua

机构信息

a School of Basic Medicine , Nanjing University of Chinese Medicine , Nanjing , Jiangsu Province , People's Republic of China.

b Library of Nanjing University of Chinese Medicine , Nanjing , Jiangsu Province , People's Republic of China.

出版信息

J Asthma. 2017 Oct;54(8):807-817. doi: 10.1080/02770903.2016.1266495. Epub 2017 Jan 19.

Abstract

OBJECTIVE

To investigate the effects of particulate matter ≤ 2.5 microns (PM2.5) on asthma-related phenotypes and on lung expression of TRPA1 and TRPV1 proteins in a mouse model of asthma.

METHODS

Female BALB/c mice were utilized to establish 28- and 42-day asthma models. Mice were sensitized with ovalbumin (OVA) and challenged with OVA, OVA plus normal saline (NS), or OVA plus PM2.5 at two doses, 1.6 or 8.0 mg kg. PM2.5 was instilled intratracheally without anesthesia. After the final OVA challenge was performed, 24 hours later, the changes in airway resistance (RI) and lung dynamic compliance (Cdyn) in response to acetylcholine chloride (ACH) were evaluated, and blood, bronchoalveolar lavage fluid (BALF) and lung tissue were taken at that time. The number of eosinophils in blood and various leukocytes in BALF were determined. Lung protein was extracted and probed for TRPA1 and TRPV1 expression. Interleukin (IL)-13, substance P (SP), prostaglandin D (PGD) and nerve growth factor (NGF) in BALF were measured by enzyme-linked immunosorbent assay.

RESULTS

PM2.5 treated mice showed significantly greater changes in the number of inflammatory cells in blood and BALF, in RI and Cdyn in response to ACH, and in lung histopathology, indicated by inflammatory cell infiltration, thickened bronchial smooth muscles and bronchial mucosa damage, compared to controls. In addition, higher expression of TRPA1 and TRPV1 in lung and IL-13, SP, PGD and NGF in BALF were seen in mice exposed to PM2.5. All effects were most pronounced in mice in the 42-day model.

CONCLUSIONS

PM2.5 exacerbates effects of asthma in this model, possibly by regulating TRPA1 and TRPV1 and the relevant neurokines.

摘要

目的

在哮喘小鼠模型中,研究直径≤2.5微米的颗粒物(PM2.5)对哮喘相关表型以及对瞬时受体电位锚蛋白1(TRPA1)和瞬时受体电位香草酸亚型1(TRPV1)蛋白肺表达的影响。

方法

利用雌性BALB/c小鼠建立28天和42天的哮喘模型。用卵清蛋白(OVA)对小鼠进行致敏,并用OVA、OVA加生理盐水(NS)或OVA加两种剂量(1.6或8.0毫克/千克)的PM2.5进行激发。在无麻醉情况下经气管内滴注PM2.5。在最后一次OVA激发24小时后,评估对氯化乙酰胆碱(ACH)反应时气道阻力(RI)和肺动态顺应性(Cdyn)的变化,并在此时采集血液、支气管肺泡灌洗液(BALF)和肺组织。测定血液中嗜酸性粒细胞数量和BALF中各种白细胞数量。提取肺蛋白并检测TRPA1和TRPV1表达。采用酶联免疫吸附测定法测量BALF中的白细胞介素(IL)-13、P物质(SP)、前列腺素D(PGD)和神经生长因子(NGF)。

结果

与对照组相比,PM2.5处理的小鼠在血液和BALF中炎症细胞数量、对ACH反应时的RI和Cdyn以及肺组织病理学方面(表现为炎症细胞浸润、支气管平滑肌增厚和支气管黏膜损伤)的变化明显更大。此外,暴露于PM2.5的小鼠肺中TRPA1和TRPV1以及BALF中IL-13、SP、PGD和NGF的表达更高。所有效应在42天模型的小鼠中最为明显。

结论

在该模型中,PM2.5可能通过调节TRPA1和TRPV1以及相关神经激肽加重哮喘效应。

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