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N-乙酰半胱氨酸减轻臭氧所致的小鼠肺部炎症反应

陈庆梓, 扶招弟, 周玉波, 周丽芬, 杨春涛, 李建华^*

广州医科大学生理学教研室，广州 511436

摘要

本研究旨在探讨抗氧化剂N-乙酰半胱氨酸(N-acetyl-L-cysteine, NAC)对臭氧(ozone, O3)暴露引起的小鼠肺部炎症反应的影响。将32只C57BL/6小鼠随机分为对照组、O3组、O3+NAC组以及NAC组。各组小鼠于第1、3、5天在1.0 ppm O3或新鲜空气中暴露3 h，每次暴露前1 h腹腔注射100 mg/kg NAC或生理盐水。末次暴露24 h后检测各组小鼠的肺组织形态学，测定支气管肺泡灌洗液(bronchoalveolar lavage fluid, BALF)中的总白细胞数、白细胞分类计数、蛋白含量，肺组织匀浆液中IL-6、IL-8以及丙二醛(malondialdehyde, MDA)含量，观察各组小鼠肺部炎症反应变化情况。Western blot检测各组小鼠肺组织匀浆液中p38 MAPK、NF-κB p65蛋白表达情况。结果显示，与对照组相比，O3组小鼠肺泡壁结构明显受损，气管及血管周围有明显的炎性细胞浸润，O3+NAC组小鼠损伤较O3组明显减轻，炎性细胞浸润明显减少。O3组BALF中白细胞总数、巨噬细胞、淋巴细胞、中性粒细胞数和总蛋白浓度及肺组织匀浆液中IL-6、IL-8、MDA含量均较对照组明显增加(P < 0.05)，O3+NAC组以上指标明显低于O3组(P < 0.05)。Western blot结果显示，O3组p38 MAPK、NF-κB p65蛋白表达水平较对照组明显增加(P < 0.05)，O3+NAC组以上指标较O3组明显降低(P < 0.05)。以上结果表明，预防性给予NAC可以减轻由O3暴露引起的肺部炎症反应，保护肺组织，这种保护作用可能与p38 MAPK、NF-κB p65信号通路有关。

关键词： N-乙酰半胱氨酸; 臭氧; 肺; 炎症

分类号：R3

[N-acetyl-L-cysteine reduces the ozone-induced lung inflammation response in mice.] [Article in Chinese]

CHEN Qing-Zi, FU Zhao-Di, ZHOU Yu-Bo, ZHOU Li-Fen, YANG Chun-Tao, LI Jian-Hua^*

Department of Physiology, Guangzhou Medical University, Guangzhou 511436, China

Abstract

In this study, we investigated the protective effect of the antioxidant N-acetyl-L-cysteine (NAC) on the lung inflammation caused by ozone (O3) exposure in mice. Thirty-two C57BL/6 mice were randomly divided into control group, O3 group, O3+NAC group and NAC group. Mice were exposed to O3 (1.0 ppm) or fresh air for 3 h on the day 1, day 3 and day 5, respectively. NAC (100 mg/kg) was intraperitoneally applied to the mice 1 h before each exposure. At 24 h after the 3-time exposure, the alveolar wall structure was severely damaged and the infiltrated inflammatory cells were apparent perivascularly and peribronchiolarly. Significant increases in the total white blood cell count, macrophage, lymphocyte and neutrophil counts, as well as total protein concentration were observed in the bronchoalveolar lavage fluid (BALF) (P < 0.05). The IL-6, IL-8 (P < 0.01) and MDA levels (P < 0.05) in the lung homogenates were elevated coherently. Administration of NAC could attenuate the alveolar wall structure damage induced by O3 exposure and reduce the amount of infiltrated inflammatory cells, total and differential leukocyte counts (P < 0.05), as well as the IL-6, IL-8 (P < 0.01) and MDA release (P < 0.05). Western blotting results showed that the O3 exposure up-regulated the p38 MAPK and NF-κB p65 protein expression in the lung tissue of mice (P < 0.05), which could be alleviated by NAC (P < 0.05). These results indicated that NAC could protect against O3-induced pulmonary inflammation in mice. The beneficial effect of NAC might be related with the p38 MAPK and NF-κB p65 signal pathway.

Key words: N-acetyl-L-cysteine; ozone; lung; inflammation

收稿日期：2016-03-10　　录用日期：2016-09-01

通讯作者：李建华　　E-mail: lijianh@hotmail.com

引用本文：

陈庆梓, 扶招弟, 周玉波, 周丽芬, 杨春涛, 李建华. N-乙酰半胱氨酸减轻臭氧所致的小鼠肺部炎症反应[J]. 生理学报 2016; 68 (6): 767-774.

CHEN Qing-Zi, FU Zhao-Di, ZHOU Yu-Bo, ZHOU Li-Fen, YANG Chun-Tao, LI Jian-Hua. [N-acetyl-L-cysteine reduces the ozone-induced lung inflammation response in mice.] [Article in Chinese]. Acta Physiol Sin 2016; 68 (6): 767-774 (in Chinese with English abstract).