纳米氧化铝致大鼠肺部急性损伤研究

摘要

Objective To make a preliminary assessment on lung inflammation and oxidative stress caused by nano-alumina particles in Wistar rats.Methods 48 healthy male Wistar rats were randomly divided into four groups according to the body weight.14,70 and 350 mg/kg of nano-alumina suspension were instilled into lung single intratracheally as test groups and NS was instilled as negative group.Lung lavage fluid (BALF)and lung tissues were collected for analysis on the 3 rd and the 28 th day after treatment;lung patho-logical changes were observed.Results (1)BALF biochemical examinations showed:on the 3 rd day after treatment,the total protein (TP)levels in MG and HG were significantly higher (P <0.05).Lactate de-hydrogenase (LDH)activity,alkaline phosphatase (AKP)activity and acid phosphatase (ACP)activity in each dose group were significantly higher (P <0.05)than those in saline group;on the 28 th day after treat-ment,in MG and HG,the alkaline phosphatase (AKP)activity was higher than that in the saline group (P <0.05);in 3 test groups,the total protein (TP)content,lactate dehydrogenase (LDH)activity and acid phosphatase (ACP)activity were higher than those in the saline group (P <0.05).(2)BALF leuko-cyte count showed:on the 3 rd day after treatment,the proportion of neutrophils were increased obviously in the MG and HG (P <0.05);on the 28 th day after treatment,the percentage of neutrophils was still higher than that in saline group (P <0.05).(3)Oxidative stress test in lung tissue showed:Compared with the saline group,on the 3 rd day after treatment,MDA content in MG and HG were increased (P <0.05).The superoxide dismutase (SOD)activity in MG and HG was lower than that in saline group (P <0.05);on the 28th day after treatment,malondialdehyde (MDA)content in HG was increased (P <0.05);superoxide dismutase (SOD)activity in HG was lower than that in saline group (P < 0.05);catalase (CAT)in each dose group showed no significant difference in activity after the exposure of 3 days and 28 days;glutathione peroxidase enzymes (GSH-Px)activity in HG were significantly lower on the 3rd day and 28th day than that in saline group (P <0.05).(4)Lung histopathology showed alveolar capillary dila-tion,inflammatory cell infiltration in bronchial cells,alveolar partial pressure,cellulose exudation,inter-stitial inflammatory cell infiltration in cats in 3 dose groups.Changes became worse with the dose increased significantly.Conclusion Nano-alumina can cause inflammation and oxidative stress in lung.%目的：初步探讨纳米氧化铝颗粒对 Wistar 大鼠肺部的急性炎症反应和氧化应激损伤。方法将48只雄性 Wistar 大鼠随机分为纳米氧化铝悬液低、中、高剂量组和生理盐水组4组，每组12只，制备纳米氧化铝悬液，按14、70和350 mg／kg 剂量分别进行单次气管滴注。染毒后3 d 和28 d 取肺部灌洗液（BALF）和肺部组织，检测生化指标、白细胞计数分类及氧化应激指标，并观察肺部病理变化。结果（1）染毒后3 d，中、高剂量组 BALF中的总蛋白（TP）含量明显升高（P ＜0．05），各剂量组乳酸脱氢酶（LDH）活性、碱性磷酸酶（AKP）活性、酸性磷酸酶（ACP）活性均较生理盐水组明显升高（P ＜0．05）；染毒后28 d，中、高剂量组 BALF 中的碱性磷酸酶（AKP）活性较生理盐水组明显增加（P ＜0．05）；各染毒组中，总蛋白（TP）含量、乳酸脱氢酶（LDH）活性、酸性磷酸酶（ACP）活性均较生理盐水组明显增加（P ＜0．05）。（2）染毒后3 d，中、高剂量组与生理盐水组相比，中性粒细胞的比例均有明显增加（P ＜0．05）。染毒后28 d，高剂量组中性粒细胞所占的比例仍高于生理盐水组，并且差异具有统计学意义（P ＜0．05）。（3）与生理盐水组比较，染毒后3 d，中、高剂量组中丙二醛（MDA）含量明显增加（P ＜0．05）。中、高剂量组中超氧化物歧化酶（SOD）活性明显降低（P ＜0．05）；染毒后28 d，高剂量组中丙二醛（MDA）含量明显增加（P ＜0．05）；高剂量组中超氧化物歧化酶（SOD）活性明显降低（P ＜0．05）；各剂量组过氧化氢酶（CAT）活性在染毒后3、28 d 均无差异；高剂量组中谷胱甘肽过氧化物酶（GSH-Px）活性在染毒后3、28 d 均明显降低（P ＜0．05）。（4）各染毒组中小鼠肺组织均出现明显的炎症改变，肺泡毛细血管扩张，支气管细胞周围有少量炎性细胞浸润，部分肺泡腔受压，有纤维素的渗出，间质有炎性细胞浸润，并随剂量的增加改变明显加重。结论纳米氧化铝可引起肺部急性炎症反应和氧化应激损伤。