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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 evaluate the pulmonary toxicokinetics of tau-MWCNTs in Kunming mice by tracheal instillation and its effect on lungs in order to evaluate the biological effects of tau-MWCNTs. Methods Healthy adult male Kunming mice were weighed and then divided into five groups according to the random number table. The doses of tau-MWCNTs were 0.125, 0.25, 0.5 and 1 mg / kg, respectively. The negative control was PBS solution. The mice were sacrificed at 1, 7, 14, and 28 d after instillation by one-time instillation method, and serological and pathological analysis was performed. The same method was injected 0.5 mg / kg ~ (14) C labeled tau-MWCNTs solution, respectively, mice were sacrificed at 1,3,7,14,21,28 d, take each of the major organ tissue digestion determination of radioactivity. Results Only the lungs were radioactive and decreased gradually with time, from (80 ± 7.7)% on day 1 after drip to (22 ± 6.9)% on day 28. Serum alkaline phosphatase and lactate dehydrogenase activity in all groups increased transiently on the 7th day after instillation, and returned to the level of the control group on the 28th day after instillation. Only 1 mg / kg serum lactate dehydrogenase (14.18 ± 1.70 μmol · s -1 · L -1) did not recover to the level of [(10.95 ± 3.51) μmol · s -1 · L -1) 1)] levels; serum angiotensin converting enzyme no significant change. Pathological findings in mice lung inflammation and hyperplasia, alveolar macrophages and some bronchial epithelial cells swallowed a large number of tau-MWCNTs. Conclusion Tracheal instillation of certain doses of water-soluble tau-MWCNTs has a slight effect on the lung of mice.