国际麻醉学与复苏杂志   2018, Issue (2): 11-11
    
小泛素样修饰化抗炎机制在低分子肝素脑保护中的作用及其研究进展
顾小飞, 李恒, 陈力勇1()
1.第三军医大学大坪医院野战外科研究所麻醉科
Small ubiquitin-related modifiers-mediated anti-inflammation is involved in neuroprotective effects of low molecular weight heparins
 全文:
摘要：

背景　低分子肝素（low molecular weight heparins, LMWH）在围手术期脑卒中对脑缺血/再灌注损伤（cerebral ischemia/reperfusion injury, CI/RI）的治疗一直存在争议，尽管近年来在肝素类抗炎作用的研究中发现LMWH能够通过抑制NF?蛳κB的活化降低炎性细胞因子生成表现出脑保护效应，但对其内在调节机制的研究一直未有明确突破，这也是其在围手术期脑卒中的防治中使用受限的原因之一。　目的　探讨LMWH脑保护作用抗炎机制的可能方向。　内容　从LMWH对NF-κB活化的影响以及小泛素样修饰（small ubiquitin-related modifier, SUMO）与NF?蛳κB活化的关系两大方面进行了综述和分析，并通过与LMWH在氧化应激下对细胞内钙离子浓度调节以及蛋白SUMO化与细胞内钙离子浓度相互影响等研究理论的串接，对LMWH在CI/RI治疗中发挥抗炎作用内在调节机制的研究提出了一种新的假想。　趋向　NF-κB的活化受SUMO直接调节抑制的理论，可能为探寻LMWH抑制NF-κB活化途径的脑保护研究带来新的突破。
关键词： 低分子肝素；　脑保护；　核因子-κB；　小泛素样修饰
Abstract:

Background　The therapeutic efficacy of low molecular weight heparins(LMWH) for cerebral ischemia/reperfusion injury(CI/RI) in patients of perioperative stroke is controversial. Although recent studies show that LMWH may exert neuroprotective effects through inhibiting the activation of NF-κB to reduce the inflammatory cytokines, the mechanisms underlying anti-inflammatory effects of LMWH remain unclear.　Objective　To review recent studies in the mechanisms underlying anti-inflammatory and neuroprotective effects of LMWH.　Content　LMWH inhibits the activation and nuclear translocation of NF-κB, reducing the levels of pro-inflammatory factors. The regulation of NF-κB signaling pathway relies on the phosphorylation of IκB and the modification by ubiquitin. Small ubiquitin-related modifiers(SUMO) modify and stabilize IκB, inhibiting the activation of NF-κB. Upregulation of SUMO has been demonstrated to confer neuroprotection in CI/RI.　Trend　Inhibition of NF-κB by SUMO could be involved in neuroprotective effects of LMWH on CI/RI.
Key words: Low molecular weight heparin;　Neuroprotection;　Nuclear factor-κB;　Small ubiquitin-related modifier