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三(2-甲基丙烯酰氧乙基)异氰尿酸酯在卵清蛋白诱导的哮喘小鼠中的加重作用及肺组织中 TRPA1、TRPV1、TRPV2 的基因和蛋白表达。

Exacerbating effects of trimellitic anhydride in ovalbumin-induced asthmatic mice and the gene and protein expressions of TRPA1, TRPV1, TRPV2 in lung tissue.

机构信息

School of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

School of Basic Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

Int Immunopharmacol. 2019 Apr;69:159-168. doi: 10.1016/j.intimp.2019.01.038. Epub 2019 Feb 1.

DOI:10.1016/j.intimp.2019.01.038
PMID:30716586
Abstract

With the increasing morbidity and mortality of asthma, asthma aggravated by environmental pollution has drawn more attention. This study investigated the exacerbating effects of trimellitic anhydride (TMA), a typical pollutant, in ovalbumin (OVA)-induced asthmatic mice and the gene and protein expressions of TRPA1, V1, V2 in lung tissue. Female BALB/c mice were respectively administered for 42 days as follow: sensitized and challenged with OVA, sensitized and challenged with TMA, sensitized with OVA and challenged with OVA plus TMA, as well as sensitized and challenged with OVA plus TMA. 24 h after the last challenge, the changes in airway resistance (RI) and lung dynamic compliance (Cdyn) were tested. The levels of the inflammatory cells in blood and bronchoalveolar lavage fluid (BALF) were determined. The gene and protein expressions of TRPA1, V1, V2 in lung tissue were examined, and levels of interleukin (IL)-4, -13, substance P (SP), prostaglandin D (PGD), nerve growth factor (NGF) in BALF and the supernatant of lung homogenate were measured. The results indicated that OVA plus TMA significantly increased the amount of inflammatory cells in blood and BALF, enhanced RI while decreased Cdyn, and aggravated lung injury. Increased gene and protein expressions of TRPA1, V1, V2 in lung tissue, level of IL-4 in the supernatant of lung homogenate, levels of IL-13, SP, PGD, NGF in BALF and the supernatant of lung homogenate were observed. It was suggested that exacerbating effects of TMA in OVA-induced asthma might be related to the regulation of TRPA1, V1, V2 and relevant neurokines.

摘要

随着哮喘发病率和死亡率的增加,环境污染诱发的哮喘受到了更多关注。本研究探讨了三(2-羟乙基)异氰尿酸酯(TMA)这一典型污染物在卵清蛋白(OVA)诱导的哮喘小鼠中的加重作用,以及 TMA 对肺组织中 TRPA1、V1、V2 基因和蛋白表达的影响。雌性 BALB/c 小鼠分别接受以下处理 42 天:OVA 致敏和激发、TMA 致敏和激发、OVA 致敏加 OVA 激发以及 OVA 致敏加 TMA 激发。末次激发后 24 小时,检测气道阻力(RI)和肺动态顺应性(Cdyn)的变化,测定血液和支气管肺泡灌洗液(BALF)中炎症细胞的水平,检测肺组织中 TRPA1、V1、V2 的基因和蛋白表达,测定 BALF 和肺匀浆上清液中白细胞介素(IL)-4、-13、P 物质(SP)、前列腺素 D(PGD)、神经生长因子(NGF)的水平。结果表明,OVA 加 TMA 显著增加了血液和 BALF 中的炎症细胞数量,升高了 RI 而降低了 Cdyn,加重了肺损伤;肺组织中 TRPA1、V1、V2 的基因和蛋白表达增加,肺匀浆上清液中 IL-4 水平、BALF 和肺匀浆上清液中 IL-13、SP、PGD、NGF 水平升高。提示 TMA 在 OVA 诱导的哮喘中的加重作用可能与 TRPA1、V1、V2 及相关神经肽的调节有关。

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