Lipocalin-2 released in response to cerebral ischaemia mediates reperfusion injury in mice.
Lipocalin-2 released in response to cerebral ischaemia mediates reperfusion injury in mice.
复制标题
lipocalin-2响应脑缺血介导小鼠的再灌注损伤。
DOI：
10.1111/jcmm.12538
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发表时间：
2015-07
影响因子：
5.3
通讯作者：
Chou WH
中科院分区：
文献类型：
--
作者：
Wang G;Weng YC;Han X;Whaley JD;McCrae KR;Chou WH
溶栓仍然是唯一有效的治疗方法，以扭转急性缺血性中风。然而，延迟治疗可能会导致严重的并发症，包括出血性转化和再灌注损伤。脂质运载蛋白-2（LCN 2）在缺血性脑卒中患者血浆中的水平升高，但其在脑卒中中的作用尚不清楚。在这里，我们表明，LCN 2急性诱导缺血性中风后的小鼠，是一个重要的介导的再灌注损伤。早在短暂性大脑中动脉闭塞（tMCAO）后1小时，就在小鼠血清中观察到LCN 2水平增加，在23小时达到峰值水平。在tMCAO后，在浸润到同侧半球的中性粒细胞以及星形胶质细胞亚群中也检测到LCN 2，但在神经元和小胶质细胞中未检测到。卒中损伤、神经功能缺损和免疫细胞浸润在tMCAO后的LCN 2基因敲除小鼠中显著减少，但在永久性MCAO（pMCAO）后没有减少。在体外，重组LCN 2蛋白诱导原代培养的神经元凋亡的剂量依赖性的方式。我们的研究结果表明，LCN 2是一种神经毒性因子分泌迅速，脑缺血，这表明其潜在的用途作为早期中风的生物标志物和新的治疗靶点，以减少中风再灌注损伤。
Thrombolysis remains the only effective therapy to reverse acute ischaemic stroke. However, delayed treatment may cause serious complications including hemorrhagic transformation and reperfusion injury. The level of lipocalin-2 (LCN2) is elevated in the plasma of ischaemic stroke patients, but its role in stroke is unknown. Here, we show that LCN2 was acutely induced in mice after ischaemic stroke and is an important mediator of reperfusion injury. Increased levels of LCN2 were observed in mouse serum as early as 1 hr after transient middle cerebral artery occlusion (tMCAO), reaching peak levels at 23 hrs. LCN2 was also detected in neutrophils infiltrating into the ipsilateral hemisphere, as well as a subset of astrocytes after tMCAO, but not in neurons and microglia. Stroke injury, neurological deficits and infiltration of immune cells were markedly diminished in LCN2 null mice after tMCAO, but not after permanent MCAO (pMCAO). In vitro, recombinant LCN2 protein induced apoptosis in primary cultured neurons in a dose-dependent manner. Our results demonstrate that LCN2 is a neurotoxic factor secreted rapidly in response to cerebral ischaemia, suggesting its potential usage as an early stroke biomarker and a novel therapeutic target to reduce stroke-reperfusion injury.