基于细菌毒性测试与小鼠肺基因转录分析的PM2.5健康效应

尽管大量流行病学和毒理学研究表明,PM_(2.5)暴露会导致一系列肺部疾病,但是其毒性机制尚不明确.本研究选取不同浓度梯度PM_(2.5)颗粒物样品进行细菌毒性评价,结果显示颗粒物的发光细菌急性毒性、遗传毒性分别为低毒和阴性.此外,采用气管灌注方法模拟小鼠呼吸暴露,研究了肺脏病理改变及差异基因表达.肺脏病理切片分析显示,PM_(2.5)暴露造成肺组织不同程度炎症反应和纤维化损伤,并呈现浓度越高、损伤程度越明显的现象.通路分析发现PM_(2.5)暴露影响到核糖体蛋白功能、脂肪酸与胆固醇代谢功能的正常表达,提示肺部炎症反应源于基因损害,其造成的损害后果可能是不可逆的.GO聚类分析发现免疫功能发生聚类富集,相关基因功能异常表达可能是造成肺部炎症的具体路径.这些发现有助于了解PM_(2.5)暴露危害路径和机制.

Health Effects of PM2.5 Based on Bacterial Toxicity Test and Transcriptional Analysis in Lungs of Mice

Although epidemiology and toxicology studies have demonstrated that exposure to ambient air particles could result in a variety of lung diseases, but the pulmonary toxicological mechanism remains obscure. In this study, the toxicity of PM_2.5 particles in different concentrations was investigated by toxicological methods, including the luminescent bacteria acute toxicity test and genotoxicity performed by SOS chromogenic reaction. The results indicated that, the acute toxicity and genotoxicity were low and negative, respectively. In addition, rats were treated with PM_2.5 suspension through intratracheal instillation, and the pathologic changes and expression of different genes in their lungs were carried out. We found that PM_2.5 exposure resulted in fibrotic changes and inflammation in the lung with the increase in PM_2.5 concentration. Pathway analysis indicated that PM_2.5 can induce pulmonary toxicity through disturbing the function of ribosomal protein, fatty acids, and cholesterol metabolism, suggesting an inflammatory reaction in the lung is caused by genetic damage and is irreversible. A gene ontology analysis revealed that abnormal expression of related genes in the immune response could be the specific pathway of lung inflammation. These findings improve our understanding of the toxicological pathway and mechanism of PM_2.5 exposure.