Deleterious effects of dihydrotestosterone on cerebral ischemic injury.

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Title：Deleterious effects of dihydrotestosterone on cerebral ischemic injury.
题目：双氢睾酮对脑缺血性损伤的毒性作用
Author：Cheng J, Alkayed NJ, Hurn PD.
Resource: J Cereb Blood Flow Metab. 2007 Feb 21; [Epub ahead of print]

Abstract：Outcome from cerebral ischemia is sexually dimorphic in many experimental models. Male animals display greater sensitivity to ischemic injury than do their female counterparts; however, the underlying mechanism is unclear.
摘要：脑缺血结局在许多实验模型中表现出了性别差异。雄性动物比它们的雌性同类对缺血性损伤表现出更大的敏感性；然而，这种现象的潜在机制仍属未知。

The present study determined if the potent and nonaromatizable androgen, dihydrotestosterone (DHT), exacerbates ischemic damage in the male rat and alters postischemic gene expression after middle cerebral artery occlusion.
新近研究对有效的未芳香化的雄激素，双氢睾酮，是否会加剧雄性大鼠的缺血损伤并改变大脑中动脉闭塞后的缺血后基因表达进行了研究。

At 22 h reperfusion, removal of androgens by castration provided protection from ischemic injury in both cortex and striatum (2,3,5-triphenyltetrazolium chloride (TTC) histology), whereas DHT replacement (50 mg subcutaneous implant) restored infarction volume to that of the intact male; testosterone (50 mg) had similar but less potent effects.
再灌注22小时时，通过阉割来去除雄激素对皮层和新纹状体的缺血性损伤都产生了保护作用（氯化三苯四唑组织学），相反的，双氢睾酮替代（50毫克皮下植入）对于完好的雄性动物也恢复了梗死面积；睾酮（50毫克）有着相似但更弱的效应。

We utilized microarray and real-time quantitative polymerase chain reaction (PCR) to identify genes differentially expressed at 6 h reperfusion in periinfarct cortex from castrated rats with or without DHT replacement.
我们利用微点阵和实时定量PCR方法在再灌注6小时时，对进行/未进行DHT替代的阉割大鼠梗死周围皮层的基因差异表达进行了鉴定。
We identify, for the first time, a number of gene candidates that are induced by DHT with or without ischemia, many of which could account for cell death through enhanced inflammation, dysregulation of blood-brain barrier and the extracellular matrix, apoptosis, and ionic imbalance.
我们首次发现，许多候选基因在有无缺血时都由DHT诱导，这其中的许多基因能够解释通过增加炎症、血脑屏障和细胞外基质失调、凋亡和离子失衡等原因产生的细胞死亡。

Our data suggest that androgens are important mediators of ischemic damage in male brain and that transcriptional mechanisms should be considered as we seek to understand innate male sensitivity to cerebral ischemia.
我们的资料表明，雄激素在雄性动物脑中是缺血性损伤的重要介质，其转录机制有可能被认为是我们试图理解的雄性动物对脑缺血的先天敏感性。