【摘要】 目的分析染矽尘大鼠早期不同时间点、以及不同染尘量支气管肺泡灌洗液（BALF）中硝酸盐/亚硝酸盐（NO₂^-/NO₃^-）、硝化酪氨酸（NT）的含量变化以及与病理变化之间的关系,探讨一氧化氮代谢产物作为矽肺早期炎性标志物的可能性。方法将Wistar大鼠随机分为对照组、15、30、60 mg/mL染矽尘实验组,每组42只。一次性气管内注入染尘,染尘后1、3、7、14、21、28 d每组分别处死7只大鼠,收集BALF,酶联免疫吸附法（ELISA）测定BALF中硝化酪氨酸,硝酸酶还原法测定NO₂^-/NO₃^-,对肺组织标本进行HE染色行病理学观察。结果在染尘后1²8 d内,各染尘组大鼠BALF中NO₂^-/NO₃^-水平明显高于对照组,差异均有统计学意义（P<0.05）;各染尘组NO₂^-/NO₃^-水平在1 d就开始增高,并在第14 d时达到高峰,随后又有所下降。观察期内,大部分时间点染尘组大鼠BALF中硝化酪氨酸水平明显高于对照组（P<0.05）,各染尘组硝化酪氨酸水平较对照组明显增加,并在第14 d时达到高峰。结论NO₂^-/NO₃^-作为矽肺早期炎性标志物具有一定的可行性。更多还原

【Abstract】 Objective To evaluate Nitrogen Monoxide metabolites（ NO₂^-/NO₃^-and nitrotyrosine） as indicators of early silicosis for association with pulmonary pathological findings of silica-exposed rats in acute inflammatory stage. Methods Wistar male rats were randomly divided into control group and three experimental groups（ dose of dust 15,30,60 mg/ml）,each group with 42 rats. Rats in the control group were treated with 1 ml normal saline by trachea instillation,whereas the rats in experimental groups were exposed to 1 ml silica suspension by one-time trachea instillation. Seven rats of each group were sacrificed after exposed to silica on the 1 th,3 th,7 th,14 th,21 th,28 th day,then bronchoalveolar lavage fluid（ BALF）was collected. The concentrations of NO₂^-/NO₃^-and nitrotyrosine in the BALF were detected with ELISA and nitrate reduction method. Pulmonary pathological findings of the four groups were observed under light microscope as well. One-way ANOVA analyses and Pearson correlation test were used for statistical analysis. Results The concentrations of NO₂^-/NO₃^-in BALF among silica-exposed groups were significantly higher than that of the control group（ P < 0. 05）. The NO₂^-/NO₃^-levels detected increased immediately on the 1 st day,reaching the peak on the 14 th day and decreased in later days after silicaexposure. NO₂^-/NO₃^-increased time was good synchronous with the inflammatory reaction process of silicosis,as well as NO₂^-/NO₃^-levels and stained dust dose had a better dose-response relationship. The levels of nitrotyrosine among silica-exposed groups were significantly higher compared with control group（ P < 0. 05）. There was no obvious relationship between the nitrotyrosine concentrations in BALF and exposure dose. Conclusion Nitrogen Monoxide metabolites NO₂^-/NO₃^-can be considered as an indicators of early silicosis.更多还原