纳米氧化铝致大鼠肺部急性损伤研究

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350mg／kg剂量分别进行单次气管滴注。染毒后3d和28d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3d，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28d，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3d，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28d，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3d，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28d，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、28d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、28d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。

Acute lung injury in rats induced by nano-alumina

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 3ra and the 28th day after treatment; lung pathological 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 dehydrogenase （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 treatment, 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 leukocyte 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 28^th 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 dilation, inflammatory cell infiltration in bronchial cells, alveolar partial pressure, cellulose exudation, interstitial 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.