不同模式PM2.5暴露下大鼠的肺泡巨噬细胞活化及其机制

朱丽娜; 杨林汇; 林本成; 石玥; 刘焕亮; 袭著革

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中国环境科学 ›› 2025, Vol. 45 ›› Issue (2) : 1099-1109.

环境毒理与健康

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

朱丽娜^1,2, 杨林汇^1,2, 林本成², 石玥², 刘焕亮², 袭著革²

作者信息 +

Activation of alveolar macrophage in rats under different modes of PM_2.5 exposure and its mechanism

ZHU Li-na^1,2, YANG Lin-hui^1,2, LIN Ben-cheng², SHI Yue², LIU Huan-liang², XI Zhu-ge²

Author information +

文章历史 +

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-qPCR测定肺组织中M2极化标志物的mRNA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mRNA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.

Abstract

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.

导出引用

朱丽娜, 杨林汇, 林本成, 石玥, 刘焕亮, 袭著革. 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[J]. 中国环境科学. 2025, 45(2): 1099-1109

ZHU Li-na, YANG Lin-hui, LIN Ben-cheng, SHI Yue, LIU Huan-liang, XI Zhu-ge. Activation of alveolar macrophage in rats under different modes of PM_2.5 exposure and its mechanism[J]. China Environmental Science. 2025, 45(2): 1099-1109

中图分类号： X171.5

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