氮杂纳米二氧化钛对肺的损伤效应

于彩霞; 陈维艳; 龙琦; 禚昌龙; 曹文斌; 刘文秀; 卢怡; 李蓉; 周紫垣; 张爱华

doi:10.13213/j.cnki.jeom.2018.17743

氮杂纳米二氧化钛对肺的损伤效应

Pulmonary injury induced by nitrogen-doped nano titanium dioxide

摘要

摘要:
目的探究新型纳米材料氮杂纳米二氧化钛（N-nTiO₂）对肺的损伤效应。

方法 42只健康SPF级SD大鼠随机分为1个空白对照组和5个N-nTiO₂暴露组，每组7只，暴露组剂量设置分别为13.64、27.27、40.91、54.55、68.18 mg/kg（以体重计，余同）。每3 d气管滴注一次，染毒28 d。肺功能仪监测气管滴注前后肺功能变化，采用多功能酶标仪测定肺泡灌洗液中总蛋白质量浓度（下称浓度）、乳酸脱氢酶活性、碱性磷酸酶活性，HE染色观察肺组织病理损伤。

结果暴露组大鼠体重增长均较空白对照组降低（P < 0.05）。54.55、68.18 mg/kg N-nTiO₂暴露组大鼠每分通气量高于空白对照组（P < 0.05），40.91 mg/kg及以上N-nTiO₂暴露组的最大呼气流量高于空白对照组（P < 0.05），68.18 mg/kg N-nTiO₂暴露组的潮气量、最大吸气流量高于空白对照组（P < 0.05）。与空白对照组相比，仅40.91 mg/kg N-nTiO₂暴露组大鼠肺泡灌洗液中总蛋白浓度增高（P < 0.05），27.27 mg/kg及以上N-nTiO₂暴露组乳酸脱氢酶活性升高（P < 0.05），54.55 mg/kg以上N-nTiO₂暴露组碱性磷酸酶活性升高（P < 0.05）。肺病理组织学检测结果显示，染毒大鼠肺组织主要表现为细胞增生、充血、炎性细胞浸润、肺阻塞、肺不张及肺实变等，且随着染毒剂量的增加，肺组织损伤程度也逐渐加重。

结论经气管滴注N-nTiO₂后会引起大鼠肺部病理损伤及肺功能降低。

Abstract:
Objective To investigate the pulmonary injury induced by novel nano materials, nitrogen-doped nano titanium dioxide (N-nTiO₂).

Methods Forty-two specific-pathogen-free SD rats were divided into one blank control group and five N-nTiO₂ groups (13.64, 27.27, 40.91, 54.55, and 68.18 mg/kg, respectively, in terms of body weight thereafter), with seven rats in each group. The rats were exposed to N-nTiO₂ by intratracheal instillation every three days and for 28 days. Lung function changes were monitored with lung function measurement instrument, the quantity of total protein and activities of lactate dehydrogenase and alkaline phosphatase in bronchoalveolar lavage fluid were measured with multi-mode enzyme-labelled meter, and the lung histopathological damage was observed using HE staining.

Results The body weight gain was less in each N-nTiO₂ group compared with the blank control group (P < 0.05). The minute ventilation volume significantly increased in the 54.55 and 68.18 mg/kg N-nTiO₂ groups compared with the blank control group (P < 0.05), the peak expiratory flow significantly increased in the 40.91 mg/kg and above N-nTiO₂ groups (P < 0.05), and the tidal volume and peak expiratory flow significantly increased in the 68.18 mg/kg N-nTiO₂ group (P < 0.05). Compared with the blank control group, the quantity of total protein significantly increased only in the 40.91 mg/kg N-nTiO₂ group (P < 0.05), the enzyme activity of lactate dehydrogenase increased in the 27.27 mg/kg and above N-nTiO₂ groups, and the enzyme activity of alkaline phosphatase increased in the 54.55 mg/kg and above N-nTiO₂ groups (P < 0.05). The results of lung histopathological examination results demonstrated that lung tissue injury was aggravated in the groups treated with higher levels of N-nTiO₂, such as cell proliferation, hypermia, and inflammatory cell infiltration, as well as lung obstruction, atelectasis, and consolidation.

Conclusion Intratracheal instillation of N-nTiO₂ may induce not only organic lesion but also lung function impairment in rats.

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