叔丁基对苯二酚对大鼠急性矽尘暴露的保护效果和机制

Protective effect and mechanism of tHBQ on acute silica dust exposure in rats

目的研究叔丁基对苯二酚（tBHQ）在大鼠急性矽尘暴露中的保护效果及可能机制。方法将无特定病原体（SPF）级雄性Wistar大鼠随机分为对照组、模型组和干预组，每组32只。模型组与干预组采用一次性非暴露气管染尘法建立大鼠矽尘模型，干预组以质量分数为1％的tBHQ溶液进行干预，对照组以1％的生理盐水进行干预，1次／d。各组分别于3、14、28、60d处死8只大鼠，用酶联免疫吸附测定（ELISA）法测定大鼠肺组织中白细胞介素（IL）．1、肿瘤坏死因子（TNF）-α、羟脯氨酸（HYP）、转化生长因子（TGF）．B含量，用比色法测定大鼠肺组织和血清中丙二醛（MDA）含量、谷胱甘肽过氧化物酶（GSH．PX）活力。结果与对照组相比，各个时间点模型组和干预组大鼠肺组织中IL-1含量均随时间延长而升高，模型组大鼠肺组织中IL-1含量在60d时达到最高，干预组大鼠肺组织中IL-1含量在28d时达到最高，除3d外差异均有统计学意义（P〈O．05）；与对照组相比，除3d外，各个时间点模型组和干预组大鼠肺组织中TNF-α含量均增加，差异均有统计学意义（P〈0．05）；与对照组相比，各个时间点模型组和干预组大鼠肺组织中HYP、TGF-β含量均随时间延长而升高，在60d时达到最高，差异有统计学意义（P〈0．05）；与模型组相比，28、60d干预组大鼠肺组织中IL-1、HYP、TGF．B含量均明显降低，差异有统计学意义（P〈0．05）；与对照组相比，各个时间点模型组和干预组大鼠肺组织和血清中MDA的含量均随着时间延长而升高，差异有统计学意义（P〈0．05）；与模型组相比，各个时间点干预组大鼠肺组织中MDA的含量均降低，差异有统计学意义（P〈0．05）；与对照组相比，各个时间点模型组和干预组大鼠肺组织和血清中GSH-PX活力均随着时间延长而降低，除3d外差异均有统计学意义（P〈0．05）。结论tBHQ的干预可以在一定程度上减轻大鼠接触矽尘的氧化应激损伤，提高机体的抗氧化损伤能力，降低肺组织IL-1、TNF-α、TGF-β、HYP的含量，对于急性矽尘接触导致的肺组织炎症和纤维化具有一定的阻碍和抑制作用。

Objective To study the protective effects and possible mechanisms of tBHQ in rats exposed to acute silica dust. Methods Male Wistar rats without specific pathogen SPF were randomly divided into control group,model group and intervention group, 32 rats for each group. Rats in the model group and the intervention group were treated with a single non exposed tracheal dust method to establish the rats exposed to silica model. The intervention group was intervened with 1% tBHQ solution, once a day. Each group 8 rats were sacrificed at 3, 14, 28, 60 d, respectively. The contents of IL-1, TNF-α, HYP, TGF-β in the lung tissue of rats were determined by enzyme linked immunosorbent assay （ELISA）, the contents of MDA and the GSH-PX activity in lung tissue and serum of rats were determined by colorimetry. Results Compared with the control group, the contents of IL-1 in the lung tissue of the model group and the intervention group at each time point increased with time, the contents of IL-1 of model group reached the maximum at 60 d, the contents of IL-1 in intervention group reached the maximum at 28 d （P〈0.05）, except 3 d. Compared with the control group, the contents of TGF-β and HYP in thelung tissue of the model group and the intervention group at 28 and 60 d increased with time and reached the maximum at 60 d （P〈0.05）. Compared with the model group at each time point,the contents of IL-1, TGF-β, HYP in the intervention group were lower than those in the model group （P〈0.05）. Compared with the control group, the contents of MDA in lung tissue and serum of rats in model group and intervention group at different time points increased with time （P〈0.05）. Compared with the control group ,the activity of GSH-PX in serum and lung tissue of rats in model group and intervention group decreased with time ,there was no significant difference in 3 d（P〈0.05 ）, compared with the control group, the activity of GSH-PX in the lung and serum tissue of in-tervenetion group was higher than model group except the 3 d （P〈0.05）. Conclusion The intervention of tBHQ can alleviate oxidative stress in rats exposed to silica dust to some extent, improve the antioxidant capacity of the body, and reduce the contents of IL-1, TNF-α, TGF-β, HYP in lung tissue, it has a certain impediment and inhibition effect on the inflammation and fibrosis caused by acute silica dust exposure.