气管滴注水溶性牛磺酸-多壁碳纳米管对小鼠肺脏的影响

Bio-effects of water soluble taurine multi-wall carbon nanotubes on lungs of mice

目的通过气管滴注昆明小鼠观察水溶性牛磺酸修饰多壁碳纳米管(tau-MWCNTs)的肺脏毒代动力学特征及其对肺脏的影响,为评价其生物学效应提供依据。方法健康成年雄性昆明小鼠,称量体重后按数字随机表法分组,每组5只,分别给予 tau-MWCNTs 剂量为0.125、0.25、0.5、1 mg/kg,阴性对照为 PBS 溶液,气管内滴注法1次性染毒,染毒后1、7、14、28 d 处死小鼠,进行血清学和病理学分析。同法注入0.5 mg/kg^(14)C 标记 tau-MWCNTs 溶液,分别在1、3、7、14、21、28 d 处死小鼠,取各主要器官组织消解测定放射性。结果只有肺有放射性,且随时间的延长逐渐降低,从滴注后1 d 的(80±7.7)%减少到28 d 的(22±6.9)%。各组小鼠血清碱性磷酸酶和乳酸脱氢酶活性在滴注后7 d 一过性升高,滴注后28 d 恢复至对照组水平;仅1 mg/kg 组血清中乳酸脱氢酶至28 d[(14.18±1.70)μmol·s^(-1)·L^(-1)]仍未恢复至对照组[(10.95±3.51)μmol·s^(-1)·L^(-1)]水平;血清血管紧张素转换酶无明显变化。病理发现各组小鼠肺内有炎症反应和增生现象,肺泡巨噬细胞和部分支气管上皮细胞吞有大量 tau-MWCNTs。结论气管滴注一定剂量水溶性 tau-MWCNTs 对小鼠肺的影响轻微。

Objective To track the translocation of water soluble taurine multi-wall carbon nanotubos （14 C-tau-MWCNTs ） in lungs of the Kunming mice and evaluate the acute lung toxicity of intratracheally instilled tau-MWCNTs in Kunming mice. Methods Healthy adult Kunming mice were randomly grouped by their body weight （5 mice in each group ）. The lungs of mice were intratracheally instilled with 0. 125, 0. 25, 0. 5 and 1 mg/kg of water soluble tau-MWCNTs and phosphate-buffered saline （PBS） as negative control. After exposure of 1, 7, 14 and 28 days, the blood and lung tissue were collected. Blood were assessed by using biochemical biomarkers of alkaline phosphatase （ALP） , lactate dehydrogenase （LDH） and angiotensin converting enzyme （ACE）. Lung tissues were assessed by histopathology. The intratracheal instillation of 14C-tau-MWCNTs was conducted in the same way, after 1, 3, 7, 14, 21, 28 days, ^14 C-activity of the samples was counted in several organs, tissues, blood and feces etc. Results ^14C-activities were detected only in lungs, and with the exposure time proceeding the radioactivity descending from （ 80 ± 7.7 ） % of the 1 ^st day to （ 22 ± 6. 9 ） % of the 28^th day. Activity of all groups of ALP and LDH went to the highest level on the 7^th day postexopsure, and back to the control level on the 28^th day post-exposure, but LDH of 1 mg/kg group[ （ 14. 18 ± 1.70） umol · s^-1 · L^-1 ] was still higher than that of control [ （ 10. 95 ± 3.51 ） umol · s^-1 · L^-1 ] after 28 days＇ exposure. There was no significant changes observed in the activity of ACE. Histopathology found that lungs of all groups presented significant increase in pulmonary inflammation, lung cell proliferation. Many tau-MWCNTs were clearly found in some alveolar macrophages and bronchial epithelial cells. Condusion Intratracheal instillation of water soluble tau-MWCNTs could induce slight bio-effects on lungs of Kunming mice.