纳米氧化铝致大鼠肺部急性损伤研究

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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。 Objective To investigate the acute inflammatory response and oxidative stress of nano-alumina particles in the lungs of Wistar rats. Methods Forty-eight male Wistar rats were randomly divided into 4 groups (n = 4, n = 12, and n = The dose of a single tracheal instillation. Pulmonary lavage fluid (BALF) and lung tissue were collected at 3d and 28d after exposure. The biochemical, leukocyte count and oxidative stress indexes were detected and pathological changes were observed. Results (1) The contents of total protein (TP) in the BALF of middle and high dose groups were significantly increased after 3d (P <0.05). The activities of LDH and AKP ) Activity and acid phosphatase (ACP) activity in BALF were significantly higher than those in saline group (P <0.05). After 28d, the activities of AKP in BALF in medium and high dose groups were significantly higher than those in saline group (P <0.05). The contents of total protein (TP), lactate dehydrogenase (LDH) and acid phosphatase (ACP) in the treated groups were significantly increased compared with the saline group (P <0.05). (2) Compared with saline group, the proportion of neutrophils in 3d, middle and high dose groups were significantly increased (P <0.05). At 28 days after exposure, the proportion of neutrophils in the high-dose group was still higher than that in the saline group (P <0.05). (3) Compared with the saline group, the content of malondialdehyde (MDA) increased obviously in 3d, middle and high dose groups (P <0.05). The activity of superoxide dismutase (SOD) in medium and high dose groups was significantly decreased (P <0.05). The content of malondialdehyde (MDA) in high dose group increased significantly (P <0.05) (P <0.05). The activity of catalase (CAT) in each dose group had no difference at 3 and 28 days after exposure. The activity of glutathione peroxidase GSH-Px) activity was significantly decreased 3 and 28 days after exposure (P <0.05). (4) The lung tissues of mice in each exposure group showed obvious inflammatory changes, alveolar capillary dilatation, a small amount of inflammatory cell infiltration around bronchial cells, partial alveolar compression, cellulose exudation and interstitial inflammation Infiltration of cells, and with the increase of dose changes significantly increased. Conclusion nano-alumina can cause acute lung inflammation and oxidative stress injury.
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