不同模式PM_(2.5)暴露下大鼠的肺泡巨噬细胞活化及其机制  

Activation of alveolar macrophage in rats under different modes of PM_(2.5) exposure and its mechanism

作　　者：朱丽娜 杨林汇 林本成 石玥 刘焕亮 袭著革 ZHU Li-na;YANG Lin-hui;LIN Ben-cheng;SHI Yue;LIU Huan-liang;XI Zhu-ge(College of Oceanography and Ecological Science,Shanghai Ocean University,Shanghai 201306,China;Military Medical Sciences Academy,Academy of Military Sciences,Tianjin 300050,China)

机构地区：[1]上海海洋大学海洋科学与生态环境学院,上海201306 [2]军事科学院军事医学研究院,天津300050

出　　处：《中国环境科学》2025年第2期1099-1109,共11页China Environmental Science

基　　金：国家重点研发计划(2017YFC0702700)。

摘　　要：为探讨长期低浓度连续与高浓度间歇两种PM_(2.5)暴露模式对大鼠肺泡巨噬细胞活化的影响,将Wistar大鼠分为三组:空白对照组、4倍浓缩PM_(2.5)连续暴露组(4FC组)和8倍浓缩PM_(2.5)间歇暴露组(8FI组).采用动物全身动态暴露系统对大鼠进行染毒,共暴露84天.HE染色法观察肺组织病理变化,比色法测定肺泡灌洗液(BALF)中氧化应激指标,RT-q PCR测定肺组织中M2极化标志物的m RNA水平,Western-blot测定肺组织中巨噬细胞活化信号通路相关蛋白表达水平.结果显示,与对照组相比,实验组大鼠出现明显的肺损伤症状,BALF中氧化指标升高.大鼠肺组织中M2极化标志物的m RNA水平增加,PI3K/AKT以及JAK1/STAT6信号通路相关蛋白表达均明显上升,且8FI组高于4FC组.由此证明,长期吸入PM_(2.5)可通过激活PI3K/AKT和JAK1/STAT6信号通路促进肺泡巨噬细胞的活化,进而造成肺损伤.且高浓度间歇吸入PM_(2.5)比低浓度连续吸入PM_(2.5)对肺部造成的损伤更为严重.在细胞水平上,进一步验证了PM_(2.5)对AMs活化及相关信号通路的影响.To explore the effects of two distinct PM_(2.5) exposure patterns on alveolar macrophages activation in rats,namely long-term low-concentration continuous exposure and high-concentration intermittent exposure.The rats were divided into three groups:a blank control group,a 4-fold concentrated PM_(2.5) continuous exposure group(4FC group)and an 8-fold concentrated PM_(2.5) intermittent exposure group(8-FI group).Exposure was facilitated using a whole-body dynamic exposure system over 84 days.The pathological changes in lung tissue were observed using hematoxylin and eosin(HE)staining.The oxidative stress indexes in bronchoalveolar lavage fluid(BALF)were determined by colorimetry.The mRNA levels of M2 polarization markers in lung tissue were measured by RT-qPCR.The protein expression levels related to the PI3K/AKT and JAK1/STAT6 signaling pathways,which are involved in macrophage activation,were assessed by Western blot.The results showed that,compared with the control group,the experimental group showed obvious symptoms of lung injury,accompanied by a significant elevation oxidation index in BALF.The mRNA levels of M2polarization marker and the protein expression of PI3K/AKT and JAK1/STAT6 signaling pathways were significantly upregulated,with the 8FI group showing higher levels than the 4FC group.These findings demonstrate that long-term inhalation of PM_(2.5) can promote the activation of alveolar macrophages via the stimulation of the PI3K/AKT and JAK1/STAT6 signaling pathways,ultimately leading to lung injury.And intermittent inhalation of PM_(2.5) with high concentration has a more serious effect on alveolar macrophages activation than continuous inhalation to low concentration.At the cellular level,the effect of PM_(2.5) on alveolar macrophages activation and related signaling pathways were further verified.

关 键 词：PM_(2.5) 动态暴露 肺泡巨噬细胞 PI3K/AKT信号通路 JAK1/STAT6信号通路 

分 类 号：X171.5[环境科学与工程—环境科学]