大剂量N-乙酰半胱氨酸对染尘大鼠肺组织的影响

Effects of high-dose N-acetylcysteine on the lung tissues of rats exposed to silica

目的 观察大剂量N-乙酰半胱氨酸（NAC）对矽肺形成过程中炎症和纤维化反应的影响.方法 将Wisar大鼠随机分为模型组、干预组、对照组,每组32只.模型组和干预组以二氧化硅结晶体诱发染尘大鼠模型,干预组以大剂量NAC进行干预.分别在染尘后的第3、7、14、28天处死8只大鼠.对大鼠肺组织进行HE染色及Masson染色,观察肺组织病理变化.用酶联免疫法（EusA）测定肺泡灌洗液中肿瘤坏死因子-α（TNF-α）和白细胞介素-8（IL-8）的含量.结果 NAC干预组病理观察显示,肺泡炎症和纤维化程度均较模型组明显减轻.与模型组（13.84±1.61、9.23±0.87、11.23±1.25、9.56±0.76）比较,第3、7、14、28天十预组肺脏系数（9.30±0.78、6.29±0.74、7.63±0.88、6.06±1.16）均明显降低.差异有统计学意义（P＜0.01.与对照组相比,各时间点模型组肺泡灌洗液中TNF-α和IL-8含量均明显升高,差异有统计学意义（P＜0.01）;与模型组相比,各时间点干预组的TNF-α和IL-8含量均明显降低,差异有统计学意义（P＜0.01）.结论 早期大剂量NAC干预能够明显减轻染尘大鼠的肺组织炎症,降低肺泡灌洗液中TNF-α和IL-8含量,抑制和延缓肺纤维化的发生.

Objective To explore the effects of high-dose N-acetylcysteine on the lung tissues of rats exposed to silica. Methods Ninety-six Wistar rats were randomly divided into model group, intervention group and control group （32 rats for each group）. The rats of model group and intervention group were exposed to silica by intratracheal infusion of silica dust suspension. The rats in the intervention group were orally given high dose N-acetylcysteine. In 3,7,14,28 days after exposure, eight rats in each group were sacrificed, respectively and the lung samples were collected. The pathological changes of lung were evaluated by HE and Masson staining methods. The levels of TNF-α and IL-8 in the BALF were detected by ELISA. Results Compared with the control group, the alveolitis and pulmonary fibrosis in the intervention group were significantly reduced. In 3,7,14,28 days after exposure, the lung/body coefficients in the intervention group were 9.30±0.78, 6.29±0.74,7.63±0.88,6.06＋1.16 respectively, which were significantly lower than those （13.84±1.61,9.23±0.87, 11.23±1.25,9.56±0.76, P〈0.01 ）in the model group （P〈0.01）. At the different time points, the levels of TNF-α and IL-8 in the BALF in the intervention group were significantly higher than those in the control group （P〈0.01）, but were significantly lower than those in the model group （P〈0.01）. Conclusion The intervention with high dose N-acetylcysteine can significantly reduce the alveolitis and the TNF-α and IL-8 levels in the BALF, therefore, inhibit and delay the development of pulmonary fibrosis of rats exposed to silicon dioxide.