Lai M, Bae S-E, Bell J E, Seckl J R, Macleod M R
Endocrinology Unit, Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
Neuropathol Appl Neurobiol. 2009 Apr;35(2):156-64. doi: 10.1111/j.1365-2990.2008.00980.x.
We have previously reported that neuronal endangerment in vitro and hypothermic transient global ischaemia in vivo each result in increased mineralocorticoid receptor (MR) expression. In both models MR induction is associated with increased neuronal survival, and blocking MR signalling reduces neuronal survival. Furthermore, transgenic overexpression of human MR promotes neuronal survival both in vitro and in vivo.
Here we have assessed whether brief periods of cerebral ischaemia in human subjects, such as occurs in cardiac arrest from which successful resuscitation is achieved, are associated with a sustained increase in hippocampal MR mRNA expression.
Human post-mortem brain sections from patients who had died in the weeks following cardiac arrest were analysed for MR mRNA expression by in situ hybridization.
Sustained upregulation of MR mRNA expression was observed in the dentate gyrus region of human hippocampus following a brief episode of cerebral ischaemia.
This confirms that MR mRNA expression is regulated following neuronal injury in human brain, and suggests that the benefits of increased MR expression seen in animal models of ischaemia may also be observed in humans.
我们之前报道过，体外神经元损伤和体内低温性短暂全脑缺血均会导致盐皮质激素受体（MR）表达增加。在这两种模型中，MR的诱导均与神经元存活率增加相关，而阻断MR信号传导则会降低神经元存活率。此外，人MR的转基因过表达在体外和体内均能促进神经元存活。
在此，我们评估了人类受试者短暂性脑缺血（如成功复苏的心脏骤停所发生的情况）是否与海马体MR mRNA表达持续增加有关。
通过原位杂交分析心脏骤停后数周内死亡患者的人类尸检脑切片中MR mRNA的表达情况。
短暂性脑缺血发作后，在人类海马体的齿状回区域观察到MR mRNA表达持续上调。
这证实了人脑神经元损伤后MR mRNA表达受到调控，并表明在缺血动物模型中观察到的MR表达增加的益处可能在人类中也会出现。
