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重复吸入阳离子胍类消毒剂引起小鼠肺的纤维化改变研究
作者:祝肖肖 孟涛 冷曙光 郑玉新 唐敬龙

摘要:

目的  探讨重复吸入暴露消毒剂聚六亚甲基胍(PHMG)气溶胶的肺损伤及其毒理学特征。方法  将30只4周龄的C57BL/6N品系的小鼠随机分为对照组和低、高剂量组,每组雌雄各5只。以实验室Ⅱ级纯水作为溶剂对照;采用超声雾化含有PHMG水溶液产生气溶胶,低、高剂量组水溶液中PHMG浓度分别为0.1(0.01%)和1 mg/ml(0.1%),超声雾化后染毒室内PHMG的浓度分别为1.03和9.09 mg/m3。对实验小鼠进行动式呼吸暴露染毒,动物每天染毒4 h,共21 d。染毒结束后,使用肺灌洗细胞计数法对暴露后肺部炎性细胞进行评估,利用病理评价、特殊染色以及免疫组化的方法对肺部纤维化的关键指标进行评价。结果  与对照组相比,高剂量组体重出现明显降低,差异有统计学意义(P<0.05);低剂量组与对照组体重差异无统计学意义(P>0.05)。低剂量组小鼠肺灌洗液中炎性细胞数目降低,肺组织病理显示肺部发生损伤,伴随早期纤维化症状(P<0.05)。高剂量组可见肺组织纤维化改变。低、高剂量组肺纤维化标志物α-SMA均明显上调(P<0.05)。结论  吸入PHMG消毒剂能够引起小鼠肺部损伤,导致肺纤维化的发生,提示我们在工业生产和日常使用过程中,需要对这种常用消毒剂进行特殊的警示,并采取呼吸防护措施。

关键词:肺纤维化;肺;毒性作用;聚六亚甲基胍;消毒剂

Abstract:

Objective  To explore the lung damage caused by repeated inhalation of polyhexamethyleneguanidine (PHMG) disinfectant aerosol and the corresponding toxicological characteristics.Methods  Thirty four-week-old mice of C57BL/6N strain were randomly divided into three groups, the control group, low-dose group, and high-dose group. Each group had 5 male mice and 5 female mice. Lab II-level purified water was used in the control group. The PHMG disinfectant aerosol was generated by using the ultrasonic atomization of the aqueous solution containing PHMG. The PHMG concentrations in the low-and high-dose groups were 0.1 mg/ml (0.01%) and 1 mg/ml (0.1%), respectively. The concentration of PHMG in the post-chemical exposure room was 1.03 mg/m3 and 9.09 mg/m3 according to the air sampler analysis. The experimental mice were exposed to the PHMG in dynamic respiratory exposure mode for 4 hours every day in 21 days. After 21-day exposure, bronchia alveolus lung fluids (BALFs) were used to evaluate the inflammatory cells in the lungs, and pathological evaluation, special staining and immunohistochemical methods were further performed to evaluate the key indicators of pulmonary fibrosis.Results  Compared to the control group, the body weight of mice in the high-dose group was significantly decreased (P<0.05), while that of mice in the low-dose group did not significantly differ (P>0.05). The number of inflammatory cells in BALFs of low-dose exposed mice was slightly reduced, and the lung tissue pathology began to show lung damage with early fibrosis symptoms (P<0.05). The pathological examination of mice in the high-dose group showed changes in pulmonary fibrosis. Immunohistochemical staining showed that pulmonary fibrosis marker, α-SMA, was significantly increased in low-dose group and high-dose group (P<0.05).Conclusion  The repeated inhalation of PHMG disinfectant could cause lung damage such as pulmonary fibrosis in mice. It could suggest that special warnings should be given to this common disinfectant and respiratory protection measures should be adopted during industrial production and daily use.

Key words: Pulmonary fibrosis;Lung;Toxic actions;Polyhexamethyleneguanide;Disinfectant

发表日期:2020/2

引用本文:

图/表:

  • 10.3760/cma.j.issn.0253-9624.2020.02.016.F001:图1 聚六亚甲基胍染毒21 d后不同暴露组小鼠的体重

    10.3760/cma.j.issn.0253-9624.2020.02.016.F001:图1 聚六亚甲基胍染毒21 d后不同暴露组小鼠的体重

  • 10.3760/cma.j.issn.0253-9624.2020.02.016.F002:图2 聚六亚甲基胍染毒21 d后不同暴露组小鼠肺灌洗液中细胞总量计数

    10.3760/cma.j.issn.0253-9624.2020.02.016.F002:图2 聚六亚甲基胍染毒21 d后不同暴露组小鼠肺灌洗液中细胞总量计数

  • 10.3760/cma.j.issn.0253-9624.2020.02.016.T001:表1 聚六亚甲基胍染毒21 d后不同暴露组小鼠肺灌洗液中的不同亚细胞计数结果(±s)

    10.3760/cma.j.issn.0253-9624.2020.02.016.T001:表1 聚六亚甲基胍染毒21 d后不同暴露组小鼠肺灌洗液中的不同亚细胞计数结果(±s)

  • 10.3760/cma.j.issn.0253-9624.2020.02.016.F003:图3 聚六亚甲基胍染毒21 d后不同暴露组小鼠肺组织病理检查结果(HE染色,200×)

    10.3760/cma.j.issn.0253-9624.2020.02.016.F003:图3 聚六亚甲基胍染毒21 d后不同暴露组小鼠肺组织病理检查结果(HE染色,200×)

  • 10.3760/cma.j.issn.0253-9624.2020.02.016.F004:图4 聚六亚甲基胍染毒21 d后不同暴露组小鼠肺组织Masson染色情况(200×)

    10.3760/cma.j.issn.0253-9624.2020.02.016.F004:图4 聚六亚甲基胍染毒21 d后不同暴露组小鼠肺组织Masson染色情况(200×)

  • 10.3760/cma.j.issn.0253-9624.2020.02.016.F005:图5 聚六亚甲基胍染毒21 d后不同暴露组小鼠肺组织α-SMA免疫组化分析结果(200×)

    10.3760/cma.j.issn.0253-9624.2020.02.016.F005:图5 聚六亚甲基胍染毒21 d后不同暴露组小鼠肺组织α-SMA免疫组化分析结果(200×)

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