大剂量N-乙酰半胱氨酸对染尘大鼠模型的抗氧化作用

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目的观察大剂量N-乙酰半胱氨酸(NAC)在矽肺形成过程中的抗氧化作用。方法 选取Wistar健康大鼠96只,随机分为模型组、预防治疗组、对照组3组,每组32只。模型组和预防治疗组均以气管滴注二氧化硅混悬液建立染尘大鼠模型,预防治疗组以大剂量N-乙酰半胱氨酸灌胃进行干预治疗,对照组给予等量的生理盐水。分别在染尘后的第3、7、14、28天分批处死大鼠取材。切取肺组织样本作病理切片,分别行苏木精-伊红(HE)染色,Masson染色,观察肺组织病理变化,并对病理切片(14d、28d)肺纤维化进行半定量评分。测定肺组织匀浆羟脯氨酸(Hyp)含量(样本碱水解法)和微量丙二醛(MDA)的含量(TBA法)。结果与模型组比较,大剂量NAC预防治疗组病理显示肺泡炎症和纤维化程度减轻,肺纤维化得分明显降低,差异有统计学意义(P<0.01)。模型组丙二醛的含量各时间点与对照组相比,均明显增高,差异有统计学意义(P<0.01),高峰位于第7天,预防治疗组丙二醛的含量均低于模型组,差异有统计学意义(P<0.01)。肺匀浆羟脯氨酸的含量比较,模型组在第7天明显升高,高峰位于第28天,与对照组相比,差异有统计学意义(P<0.01),预防治疗组低于模型组,差异有统计学意义(P<0.01)。结论 早期应用大剂量NAC可增强肺组织的抗氧化作用,减轻二氧化硅对大鼠肺组织的损伤,部分抑制肺间质纤维化。 Objective To observe the anti-oxidative effect of high-dose N-acetylcysteine ​​(NAC) in silicosis. Methods Ninety-six healthy Wistar rats were randomly divided into model group, prophylaxis group and control group with 32 rats in each group. Model group and prophylaxis group were established by tracheal instillation of silica suspension stained model rats, prophylaxis treatment group with high-dose N-acetyl cysteine ​​gavage intervention treatment, the control group was given the same amount of physiology brine. Rats were sacrificed in batches on the 3rd, 7th, 14th and 28th days after the infection respectively. The lung tissue samples were taken for pathological sections. The hematoxylin and eosin (HE) staining and Masson staining were respectively performed to observe the histopathological changes in the lung tissue. The pulmonary fibrosis scores of the pathological sections (14d, 28d) were semi-quantitatively scored. The contents of hydroxyproline (alkaline hydrolysis) and trace amounts of malondialdehyde (MDA) in lung homogenate (TBA method) were determined. Results Compared with the model group, the pathology of the high-dose NAC prophylaxis group showed that alveolar inflammation and fibrosis were relieved, and pulmonary fibrosis scores were significantly lower (P <0.01). The content of malondialdehyde in model group at each time point was significantly higher than that in control group, the difference was statistically significant (P <0.01), the peak was on the seventh day, and the content of malondialdehyde in prevention and treatment group was lower than that in model group , The difference was statistically significant (P <0.01). Compared with the control group, the content of hydroxyproline in the lung homogenate was significantly increased in the model group on the 7th day and the peak on the 28th day (P <0.01), and was lower in the preventive treatment group than in the model group Group, the difference was statistically significant (P <0.01). Conclusion Early application of high-dose NAC can enhance the anti-oxidative effect of lung tissue, reduce the damage of silica on rat lung tissue, and partially inhibit pulmonary interstitial fibrosis.
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