杨正丽, 邵乃敏, 丁瑜, 徐菁, 刘君丽, 刘玺, 钱科蕾, 洪新宇. 吸入聚六亚甲基胍消毒剂气溶胶对小鼠免疫器官和免疫细胞的影响[J]. 环境与职业医学, 2024, 41(8): 855-860, 866. DOI: 10.11836/JEOM24021
引用本文: 杨正丽, 邵乃敏, 丁瑜, 徐菁, 刘君丽, 刘玺, 钱科蕾, 洪新宇. 吸入聚六亚甲基胍消毒剂气溶胶对小鼠免疫器官和免疫细胞的影响[J]. 环境与职业医学, 2024, 41(8): 855-860, 866. DOI: 10.11836/JEOM24021
YANG Zhengli, SHAO Naimin, DING Yu, XU Jing, LIU Junli, LIU Xi, QIAN Kelei, HONG Xinyu. Effects of inhalation of polyhexamethylene guanidine disinfectant aerosol on immune organs and immune cells in mice[J]. Journal of Environmental and Occupational Medicine, 2024, 41(8): 855-860, 866. DOI: 10.11836/JEOM24021
Citation: YANG Zhengli, SHAO Naimin, DING Yu, XU Jing, LIU Junli, LIU Xi, QIAN Kelei, HONG Xinyu. Effects of inhalation of polyhexamethylene guanidine disinfectant aerosol on immune organs and immune cells in mice[J]. Journal of Environmental and Occupational Medicine, 2024, 41(8): 855-860, 866. DOI: 10.11836/JEOM24021

吸入聚六亚甲基胍消毒剂气溶胶对小鼠免疫器官和免疫细胞的影响

Effects of inhalation of polyhexamethylene guanidine disinfectant aerosol on immune organs and immune cells in mice

  • 摘要:
    背景 自加湿器消毒剂事件后,吸入聚六亚甲基胍(PHMG)的呼吸毒性被广泛研究,而其免疫毒性的研究尚不全面。
    目的 探究吸入PHMG消毒剂气溶胶对小鼠主要免疫器官及免疫细胞的影响。
    方法 将30只6~8周雄性C57BL/6J小鼠随机分成对照组、低剂量组(0.1 mg·m−3 PHMG)和高剂量组(1.0 mg·m−3 PHMG)3组,每组10只。采用口鼻动式吸入染毒方式,每天吸入4 h,每周5 d,连续4周。染毒结束后,采集小鼠眼内眦静脉血,用动物血液细胞分析仪测定小鼠外周血液学指标,而后颈椎脱臼法处死小鼠,分离肺、胸腺、脾脏和股骨,对肺、胸腺、脾脏称重并计算脏器系数,将胸腺、脾脏以及骨髓制备成单细胞悬液,用流式细胞仪检测其淋巴细胞的分型及比例。
    结果 染毒第7天起,高剂量组小鼠体重低于对照组小鼠体重(P<0.01);染毒结束时,与对照组小鼠体重相比,高剂量组小鼠体重减少了15.74%(P<0.01)。低剂量组和高剂量组肺脏系数均高于对照组(P<0.01),高剂量组小鼠胸腺系数低于对照组(P<0.05),脾脏系数无明显变化(P>0.05)。高剂量组小鼠外周血中白细胞数量(1.49±0.22)×109·L−1、淋巴细胞数量(0.96±0.36)×109·L−1及其比例(63.13±14.96)%均低于对照组(2.69±0.25)×109·L−1、(2.33±0.28)×109·L−1、(86.23±3.40)%(P<0.01),而高剂量组小鼠外周血中红细胞数量(12.32±0.46)×1012·L−1、血红蛋白数量(175.25±4.65)g·L−1和血细胞比容(53.55±0.70)%均高于对照组(11.11±0.37)×1012·L−1、(160.67±4.04)g·L−1、(45.10±9.75)%(P<0.05)。与对照组比较,高剂量组小鼠胸腺中CD4+ CD8+双阳性T细胞比例降低(P<0.05),CD4+ T细胞和CD8+ T细胞比例升高(P<0.05),CD8+、CD4+ CD8+、CD4+、CD4- CD8-细胞数量均降低(P<0.05),脾脏中CD4+ T细胞比例升高(P<0.05),骨髓中T细胞、CD4+ T细胞和CD8+ T细胞比例及数量均升高(P<0.05)。
    结论 吸入PHMG可使小鼠胸腺萎缩,扰乱T淋巴细胞发育进程,导致骨髓、外周血和脾脏中免疫细胞数量失衡,表明吸入PHMG可诱导机体免疫紊乱。

     

    Abstract:
    Background The respiratory toxicity of inhaled polyhexamethylene guanidine (PHMG) has been extensively studied since the humidifier disinfectant incident. However, the impacts of inhalation of PHMG on the immune system are not comprehensively studied yet.
    Objective To explore the effects of inhalation of PHMG disinfectant aerosol on major immune organs and immune cells in mice.
    Methods Thirty male C57BL/6J mice (6-8 weeks old) were randomly divided into three groups: control, low-dose (0.1 mg·m−3 PHMG), and high-dose (1.0 mg·m−3 PHMG), with ten mice in each group. The mice were administered by oral-nasal inhalation of PHMG aerosol for 4 h per day, 5 d per week for 4 weeks consecutively. After designed treatment, venous blood was collected from the inner canthus of the eyes of mice and peripheral hematological indicators were measured with a blood analyzer. Then the mice were sacrificed by cervical dislocation and the lung, thymus, spleen, and femur were isolated. Lung, thymus, and spleen were weighed and organ coefficients were calculated, and single cell suspensions of thymus, spleen, and bone marrow were prepared to analyze lymphocytes phenotypes and proportions by flow cytometry.
    Results The body weight of mice in the high-dose group was lower than that of mice in the control group (P<0.01) from the 7th day of inhalation, and decreased by 15.74% compared with that of mice in the control group at the end of inhalation (P<0.01). The lung coefficients of both the low-dose and high-dose groups were higher than that of the control group (P<0.01), the thymus coefficient of mice in the high-dose group was lower than that of the control group (P<0.05), but the spleen coefficient did not change significantly (P>0.05). Leukocyte count (1.49±0.22)×109·L−1, lymphocyte count (0.96±0.36)×109·L−1 and its proportion (63.13±14.96)% in the peripheral blood of mice in the high-dose group were lower than those in the control group (2.69±0.25)×109·L−1, (2.33±0.28)×109·L−1, and (86.23±3.40)%, respectively (P<0.01), whereas red blood cell count (12.32±0.46)×1012·L−1, hemoglobin count (175.25±4.65) g·L−1, and hematocrit (53.55±0.70)% in the peripheral blood of mice in the high-dose group were higher than those in the control group (11.11±0.37)×1012·L−1, (160.67±4.04) g·L−1, and (45.10±9.75)%, respectively (P<0.05). Compared with the control group, the proportion of CD4+ CD8+ double-positive T cells decreased (P<0.05), the proportions of CD4+ T cells and CD8+ T cells increased (P<0.05), and the amounts of CD8+, CD4+ CD8+, CD4+, and CD4- CD8- cells decreased (P<0.05) in the thymus of mice of the high-dose group, the proportion of CD4+ T cells in the spleen of the high-dose group increased (P<0.05), the proportions and amounts of T cells, CD4+ T cells, and CD8+ T cells in the bone marrow of the high-dose group increased (P<0.05).
    Conclusion Inhalation of PHMG may cause thymic atrophy, disrupt T-lymphocyte development, and lead to an imbalance in the number of immune cells in the bone marrow, peripheral blood, and spleen, suggesting that inhalation of PHMG induces immune dysfunction.

     

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