Xue Zhaohui, Li Ang, Zhang Xueya, Yu Wancong, Wang Junyu, Zhang Yixia, Gao Xin, Kou Xiaohong
School of Chemical Engineering and Technology, Tianjin University Tianjin 300072 China
Medical Plant Lab, Tianjin Research Center of Agricultural Biotechnology Tianjin 300381 China.
RSC Adv. 2019 Apr 15;9(21):11707-11717. doi: 10.1039/c9ra00252a. eCollection 2019 Apr 12.
Haze pollution has become a global environmental problem, subsequently affecting air quality, climate, economy and human health. Notably, PM (particulate matter with an aerodynamic diameter less than 2.5 micrometers) significantly accounts for a variety of adverse health effects, in particular pulmonary diseases such as asthma and lung cancer. Clinical diagnosis and medical treatment of the lung damage caused by PM still remain significant challenges due to the lack of specific biomarkers and pathways. Here, we established a rat model of nonsurgical intratracheal instillation to investigate PM exposure and employed iTRAQ based analytical technique and bioinformatics tools to identify putative biomarkers and pathways. We identified 163 differentially expressed proteins (DEPs). Among these proteins, we screened six DEPs (HMOX1, MP2K5, XRCC1 E9PTZ7, KNT2 and A1AG) as the putative biomarkers, with significant differentially expressed levels (percentage increment > 140%). Pathway analysis indicated that calcium signaling, MAPK and PI3K/AKT might be involved in the process of PM-induced lung damage. Western-blotting was used to verify DEPs in the AEC-II cell model for early diagnosis. In summary, our data can serve as fundamental research clues for further studies of PM-induced toxicity in the lungs.
雾霾污染已成为全球性环境问题，进而影响空气质量、气候、经济和人类健康。值得注意的是，细颗粒物（空气动力学直径小于2.5微米的颗粒物）是导致各种不良健康影响的重要因素，尤其是引发哮喘和肺癌等肺部疾病。由于缺乏特异性生物标志物和相关途径，对细颗粒物所致肺损伤的临床诊断和治疗仍然面临重大挑战。在此，我们建立了非手术气管内滴注大鼠模型以研究细颗粒物暴露情况，并采用基于iTRAQ的分析技术和生物信息学工具来鉴定潜在的生物标志物和相关途径。我们鉴定出163种差异表达蛋白（DEPs）。在这些蛋白中，我们筛选出六种差异表达蛋白（血红素加氧酶1、丝裂原活化蛋白激酶磷酸酶5、X射线修复交叉互补蛋白1、角蛋白2、激肽原1和α1抗胰蛋白酶）作为潜在生物标志物，其差异表达水平显著（百分比增量>140%）。通路分析表明，钙信号传导、丝裂原活化蛋白激酶和磷脂酰肌醇-3-激酶/蛋白激酶B信号通路可能参与了细颗粒物诱导的肺损伤过程。利用蛋白质免疫印迹法在肺泡Ⅱ型上皮细胞模型中验证差异表达蛋白以进行早期诊断。总之，我们的数据可为进一步研究细颗粒物诱导的肺毒性提供基础研究线索。
