LPS诱发急性肺损伤中miR-16的表达及功能研究

目的观察脂多糖（LPS）诱发的急性肺损伤中microRNA-16（miR-16）的表达变化及其对炎症因子TNF-α等表达的调节。方法通过生物信息学分析不同物种间miR-16基因序列的保守性。通过小鼠气道向其肺内注入LPS（10 mg.kg-1）,构建小鼠急性肺损伤模型,采用实时荧光定量PCR分析miR-16、IL-6、TNF-α的表达水平;在培养的肺上皮细胞A549中采用miR-16 mi mic对miR-16进行过表达研究。结果 miR-16基因序列在斑马鱼、大鼠、小鼠和人中序列高度保守;miR-16在急性肺损伤病理过程中表达明显降低（P〈0.05）;A549细胞中miR-16的表达水平显著升高（P〈0.01）,相反,LPS诱导的炎症因子IL-6、TNF-α的表达水平显著降低（P〈0.05）。结论 miR-16在LPS诱发的急性肺损伤病理过程中的表达降低,miR-16过表达能够显著抑制LPS对炎症的诱发作用,表明miR-16在急性肺损伤的炎症发生过程中发挥着重要功能。

Expression and Function of miR-16 in Lipopolysaccharide-induced Acute Lung Injury

Objective To observe the expression of microRNA-16（miR-16） in lipopolysaccharide（LPS）-induced acute lung injury and to explore the role of miR-16 in the regulation of inflammatory cytokine expression.Methods The sequences of miR-16 were analyzed by using bioinformatics.LPS（10 mg·kg-1）was intratracheally administered to induce acute lung injury in mice.A549 cells were transfected with miRNA mimic to explore the effect of miR-16 on inflammatory reaction.The levels of miR-16,IL-6 and TNF-ɑ expression were determined by real-time PCR.Results MiR-16 was evolutionarily conserved in zebrafish,rats,mice and humans.In LPS-induced lung injury model,miR-16 expression was profoundly down-regulated（P0.05）.Over-expression of miR-16（P0.01）in A549 cells significantly inhibited the expression of IL-6 and TNF-ɑ（P0.05）.Conclusion MiR-16 is aberrantly expressed in LPS-induced lung injury and over-expression of miR-16 inhibits inflammatory reaction induced by LPS in A549 cells,indicating that miR-16 play an important role in inflammation following acute lung injury.