叔丁基对苯二酚对矽尘暴露大鼠肺脏病理变化及机制研究

目的 探讨叔丁基对苯二酚对矽尘暴露大鼠肺脏病理改变的影响及可能机制。方法 96只Wistar大鼠随机分为对照组、模型组和干预组，每组32只。对照组气管灌注1mL 0.9%NaCL溶液；模型组气管灌注150mg/mL二氧化硅粉尘悬浮液1mL（0.9%NaCL稀释）；干预组同模型组方式染尘，24h后每天经口灌胃给予质量比1%叔丁基对苯二酚溶液1mL。染尘后3d、14d、28d、60d处死大鼠，HE、Masson染色评价肺组织病理学变化。Western blot检测肺组织血红素加氧酶-1(HO-1)、核因子E2相关因子2(Nrf2)蛋白表达。结果 矽尘暴露后大鼠肺组织炎症和纤维化程度明显升高，部分出现片状纤维斑；干预28d、60d组肺组织纤维化评分显著低于同期模型组（P<0.05）。与对照组比较，模型组和干预组HO-1蛋白表达显著升高（P<0.05）。随染尘时间延长，核内Nrf2蛋白表达呈上升趋势，而胞浆内则呈现降低趋势。结论 叔丁基对苯二酚可能通过激活Nrf2/ARE信号通路对矽尘暴露大鼠肺组织起到保护作用，延缓炎症及纤维化程度。

Pathological changes and mechanism of tert-butyl hydroquinone on lung of rats exposed to silica dust

To investigate the effect and its mechanism of tert － butyl hydroquinone on lung pathological changes by silica dust in rats. Methods 96 Wistar rats were randomly divided into control group，model group and intervention group，and there were 32 rats in each group. The control group was given 1 ml 0. 9% NaCl solution by tracheal perfusion，and the model group was given 150 mg /ml silica dust suspension 1 ml ( 0. 9% NaCl dilution) . The intervention group received the same treatment as the model group. And the intervention group were given 1% t BHQ solution orally every day after 24 hours. The rats were executed after 3，14，28 and 60 days. The pathological changes of lung tissue were evaluated by hematoxylin － eosin( HE) and Mass on staining. Western blot was used to detect the expression of HO － 1 and Nrf2 in lung tissue. Ｒesults The degree of inflammation and fibrosis in rats exposed to silica dust was significantly increased，and some of them showed flaky fibrous plaques. The fibrosis scores in the intervention group of 28 days and 60 days were significantly lower than the scores in the model group at the same time ( P ＜ 0. 05) . Compared with the control group，HO － 1 protein expression was significantly increased in the model group and the intervention group ( P ＜ 0. 05) . With the prolonged dusting time，the expression of Nrf2 protein in the nucleus showed an upward trend，while the cytoplasm showed a downward trend. Conclusion Tert － butylhydroquinone may play a protective role in the lung tissue of rats that are exposed to silica dust by activating the Nrf2 /ARE signaling pathway，and delay the degree of inflammation and fibrosis.