多壁碳纳米管对小鼠肺脏的损伤
Bio-effects of Multi-wall Carbon Nanotubes on Lungs of Mice
-
摘要:
目的 观察多壁碳纳米管(multiwalled carbon nanotubes,MWCNTs)对肺脏的影响,为评价其生物学效应及安全性提供依据。 方法 健康成年雄性ICR小鼠138只,按体重随机均分为3大组,各大组下设:空白对照组和溶剂对照组,每组5只;阳性对照二氧化硅(SiO2)设2个剂量组,染毒剂量分别为0.05、0.40 mg/kg体重,每组6只;MWCNTs染毒设4个剂量组,染毒剂量分别为0.05、0.10、0.20、0.40 mg/kg体重,每组6只。暴露式气管内滴注法一次性染毒,染毒1、7、28 d后分别处死1大组动物,进行肺脏器系数、肺灌洗液各指标以及肺病理分析。 结果 ①MWCNTs各组:肺脏器系数以染毒1 d最高,随后降低,染毒28 d恢复至溶剂对照组水平;肺灌洗液总蛋白、反映肺泡Ⅱ型上皮细胞损伤的碱性磷酸酶(AKP)活性和反映肺巨噬细胞受损的乳酸脱氢酶(LDH)活性均呈染毒1 d最高后逐渐降低趋势。②各阳性对照组:染毒1 d和7 d肺脏器系数均低于MWCNTs染毒组,但染毒28 d明显高于MWCNTs组;肺灌洗液中总蛋白呈先降低再升高趋势,至染毒28d高于相应剂量MWCNTs组;AKP活性先升高至染毒28d基本恢复正常;LDH活性至染毒28d未恢复正常。③病理观察:MWCNTs组和阳性对照组肺内有炎症反应和增生现象,MWCNTs组肺泡巨噬细胞和部分支气管上皮细胞吞噬有大量MWCNTs。SiO2各组因材料本身无色没有观察到沉积,但均发现较严重的炎症反应和渗出增生等改变,正常肺泡结构消失,伴有一些肺泡代偿性肺气肿,且到染毒28 d时炎症反应无减轻的趋势。 结论 气管滴注MWCNTs引起小鼠肺脏损伤,但是这种损伤随着时间的延长逐渐减轻,MWCNTs与SiO2致肺脏损伤的表现不同,其损伤机制可能也不同。 Abstract:Objective To investigate the injury on lungs of the Institute for Cancer Research(ICR) mice after in tratracheally instilled multiwalled carbon nanotubes(MWCNTs), and provide a basis for evaluating its biological effects and exploring toxicity mechanisms. Methods A total of 138 healthy adult ICR mice were randomly grouped by their body weight. Eight groups were employed. Phosphate-buffered saline (PBS)was used for solvent control and nothing for blank control with 5 mice in each group. Two dose groups (0.05 and 0.40 mg/kg body weight)of SiO2 were used as positive control with 6 mice in each group and four dose groups (0.05, 0.10, 0.20, and 0.40 mg/kg body weight)of MWCNTs as exposure groups with 6 mice in each group. Mice were intoxicated by intratracheal instillation once separately. On 1, 7 and 28 d after the instillation, mice were sacrificed and indices of lung injury in lung homogenate and bronchoalveolar lavage fluid (BALF)were determined respectively, and lung tissues were observed by histopathology. Results The lung weight ratio of each exposure group showed a high tendency on the first day and then decreased, and resumed to the level of control on the 28 d group. The total protein, alkline phosphatase (AKP)and lactate dehydrogenase (LDH)in the BALF were relatively higher compared with the solvent control in the 1 d group and gradually decreased over the time. The lung weight ratios of the SiO2 control groups were lower than the MWCNTs groups on the 1 d and 7 d and then became higher on the 28 d. Histopathology observation showed that lungs of all exposure groups and positive control groups presented significant pulmonary inflammation and lung cell proliferation.Many MWCNTs were clearly found in some alveolar macrophages and bronchial epithelial cells in the exposure groups. Conclusion Intratracheal in stillation of MWCNTs could induce injury on lungs of ICR mice, but the damage became less severe as time passed by. There were different lung injuries between MWCNTs and SiO2 groups, the possible mechanism of lung injury might be different.
下载:
