阻断 NF -κB 信号途径防治急性肺损伤的研究进展

Research advances in controlling acute lung injury by blocking the NF-κB signal pathways

目的：探讨以核因子κB（NF-κB）为靶点防治急性肺损伤（ALI）的分子生物学机制。方法应用CNKI、Medline、ScienceDirect 等数据库，查阅近年来相关文献，总结NF-κB在ALI中的作用机制与干预手段。结果 NF-κB在ALI中的信号转导途径及作用机制逐渐被揭示，大量研究证实，通过干预NF-κB上游信号通路、NF-κB抑制蛋白（ IκB）、IκB激酶（ IKK）等途径，能在一定限度内阻断细胞因子和炎症介质的释放，缓解ALI的炎症反应。结论阻断靶细胞中NF-κB通路、特异性抑制目的蛋白和基因表达，或许能成为未来治疗ALI的研究方向；不恰当的药物干预会破坏机体的免疫平衡状态，虽然NF-κB阻断剂已进入临床试验阶段，但多数仅局限于动物实验和细胞水平，实现临床防治尚需进行大量实验研究。

Objective To study the molecular biology mechanism of nuclear factor κB （ NF-κB） and its expression in acute lung injury （ ALI ） by reviewing the latest research progress in the prevention and control of NF -κB targets in ALI, and to provide reference to research for blocking NF -κB signal pathway in the prevention and control of ALI .Methods We searched CNKI , Medline, ScienceDirect database , reviewed the relevant literatures in recent years , and summarized the mechanism and intervention of NF -κB pathway in ALI .Results The mechanism of NF -κB signal pathway in ALI has begun to be understood .A growing body of evidence has shown that the intervention of the upstream signals of NF -κB pathway, the NF-κB inhibiting protein （ IκB） and IκB kinase （ IKK） to some extent can block the release of inflammatory mediators and therefore alleviate inflammatory reaction of ALI.Conclusion NF-κB pathway plays an important role in the process of ALI .Blocking NF-κB pathway can reduce signal inflammatory mediators and the release of cell factors , consequently reducing inflammatory reaction .But nonspecific drug intervention will also destroy the balance of the body .Future investigations should focus on how to block the specific target cell and specific inhibition of protein expression of NF-κB pathway.At present, although some of the NF-κB blockers have entered into the phase of clinical trials , most of them are restricted to animal experiment and cellular level .For the realization of blocking NF -κB pathway approach applied to clinical ALI treatment , we still need a large number of experimental investigations .