大剂量N-乙酰半胱氨酸对染尘大鼠模型的抗氧化作用

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。

Antioxidant effects of oral N-acetylcysteine on silica-exposed rats

Objective To examine the antioxidant therapy effects of oral N-acetylcysteine（NAC） in silica-exposed rats.Methods A total of 96 Wistar rats were randomly divided into groups of silica-exposed only（model）,silica-exposed and NAC treated and healthy control.The dose of 500mg·kg-1 NAC was orally given to Wistar rats once a day from one week prior to the single intratracheal instillation of silica dust suspension（model and treatment groups） or saline（control group）.NAC treatment was continued 2 days after the instillation of silica dust.The lung samples of rats were collected in the 3rd,7th,14th and 28th day of silica post-instillation.The pathological changes of lung tissues were evaluated by the methods of HE and Masson staining.The extent of alveolar fibrosis was assessed by the semi-quantitative histological scores of Ashcroft method.The contents of hydroxyproline（HYP） and malondialdehyde（MDA） in lung tissue were measured per manufacturer′s instruction.Results The pathological changes of alveolitis and pulmonary fibrosis were mitigated in the rats of treated group compared with that in the rats of model group.The semi-quantitative scores of histological assessment showed less collagen deposition in the rats of treated group than in the rats of model group（P0.01）.The level of MDA in model group increased significantly at all tested time points（P0.01） and the maximum value appeared in the 7th day of silica post-instillation.The level of HYP increased from the 7th day and the maximum value appeared in the 28th day of silica post-instillation in model group（P0.01）.The contents of HYP and MDA decreased significantly in the lung tissues of treated group at different tested time points（all P0.01）.Conclusion Oral N-acetylcysteine improves pulmonary antioxidant effects and reduces silica-exposed lung damages in rats.