摘要
目的探索miR-144在纳米二氧化硅（SiO2）致大鼠肺损伤中的生物学作用。方法150只健康雄性SD大鼠随机分生理盐水对照组和6．25、12．5、25．0mg／ml纳米SiO2组及25．0mg／ml微米SiO2组，每组30只，分别于染尘7、15、30、60、90d后各处死6只，观察各时间点大鼠肺组织的病理改变。用实时荧光定量聚合酶链式反应（qRT-PCR）法检测大鼠经气管一次性灌注25mg／ml纳米SiO290d后肺组织中miR．144的表达水平；用Targetscan、microRNA．org及miRDB3个数据库对miR．144进行靶基因预测；用theGeneOntology、KEGG分别对预测靶基因进行功能显著性富集分析和信号通路分析，筛选与肺纤维化相关的靶基因。结果25．0mg／ml纳米SiO2染尘90d组大鼠肺组织中miR-144表达上调，与Hiseq2000高通量测序的结果一致；筛选miR-144的预测靶基因为SMAD4、SMAD5、ADAMTS3、ADAMTS15、ADAMTS19等，这些基因可能与纤维化相关或参与纤维化通路。结论miR-144可能参与肺纤维化的调控，在纳米SiO2所致肺损伤中发挥一定作用。
Objective To Investigate the biological effects of miR-144 in rats＇ pulmanory injury induced by nanosized SiO2 preliminarily. Method 150 healthy SD rats were divided into five groups randomly： the control group, the nanosized SiO2 groups of 6.25, 12.5, 25.0 mg/ml, and the microsized SiO2 group of 25.0 mg/ml, 30 rats each group. Six rats were sacrificed for their pathological change on the 7th, 15th, 30th, 60th and 90th day after exposure. The expression levels of mature miR-144 in lung tissue of the rats after instilled intracheally nanosized SiO2 at 90d was detected by Quantitative Reverse Transcription PCR. Target prediction for miR-144 was conducted by databases of Target-scan, microRNA.org and miRDB. Function-significant enrichment analysis and signal pathway analysis for predicted target genes were respectively conducted by the Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes, then target genes related to pulmonary fibrosis were screened out. Results The expression of miR-144 was up-regulated in lung tissue of rats exposed to nanosized SiO2. The result was consistent with the results of high-throughput sequencing Hiseq 2000. The target genes of miR-144 related to fibrosis or signal pathway involved in fibrosis were screened out.They are SMAD4, SMAD5, ADAMTS3, ADAMTS15 and ADAMTS19. Conclusion MiR-144 probably participate in the regulation of fibrosis, which may play an important role in pulmonary injury induced by nanosized SiO2.
出处
《中华劳动卫生职业病杂志》
CAS
CSCD
2015年第9期641-645,共5页
Chinese Journal of Industrial Hygiene and Occupational Diseases
基金
国家自然科学基金面上项目（81273046）
国家重大科学研究计划项目（2011CB933404）
江苏省预防医学科研课题（Y2012039）
环境医学工程教育部重点实验室开放课题基金（2011EME009）
