Potential role for heat shock protein 72 in antagonizing cerebral vasospasm after rat subarachnoid hemorrhage
Potential role for heat shock protein 72 in antagonizing cerebral vasospasm after rat subarachnoid hemorrhage
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DOI：
10.1161/01.cir.0000142615.88444.31
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发表时间：
2004-09-28
期刊：
影响因子：
37.8
通讯作者：
Tanaka, T
中科院分区：
文献类型：
--
作者：
Nikaido, H;Tsunoda, H;Tanaka, T
脑血管痉挛是自发性蛛网膜下腔出血（SAH）后发生的迟发性脑动脉狭窄。尽管有大量的实验和临床研究，血管痉挛的确切病理生理学仍然未知。使用荧光差异显示系统，我们已经确定了编码热休克蛋白72（HSP 72）的基因被脑血管痉挛高度上调。因此，我们阐明了在大鼠实验性SAHmodel.Methods和Results-By血管造影，脑血管痉挛的HSP 72基因的作用，从第1天检测到，最大的缩小检测到第2天。脑池内注射HSP 72反义寡核苷酸可特异性抑制HSP 72基因表达，并在血管造影研究的第2天和第3天显著加重脑血管痉挛。口服给药的geranylgeranylacetone（GGA），一种抗溃疡药物，增强HSP 72的诱导和减少cerebral vasospassion. Conclusions-这些结果表明，HSP 72在拮抗迟发性脑血管痉挛后SAH和GGA提供了对迟发性脑血管痉挛的保护作用，至少部分通过诱导HSP 72。
Background-Cerebral vasospasm can be defined as delayed-onset narrowing of the cerebral arteries that can occur after a spontaneous aneurysmal subarachnoid hemorrhage (SAH). Despite a large number of experimental and clinical investigations, the exact pathophysiology of vasospasm remains unknown. Using a fluorescence differential-display system, we have identified the gene encoding heat shock protein 72 (HSP72) as being highly upregulated by cerebral vasospasm. We therefore elucidated the role of the HSP72 gene in cerebral vasospasm in a rat experimental SAH model.Methods and Results-By angiography, cerebral vasospasm was detected from day 1, with maximal narrowing detected on day 2. Intracisternal injection of antisense HSP72 oligodeoxynucleotide led to specific inhibition of HSP72 gene expression and significantly aggravated cerebral vasospasm on days 2 and 3 of the angiographic studies. Oral administration of geranylgeranylacetone (GGA), an antiulcer drug, enhanced HSP72 induction and reduced cerebral vasospasm.Conclusions-These results suggest HSP72 plays a novel role in antagonizing delayed cerebral vasospasm after SAH and that GGA provides protective effects against delayed cerebral vasospasm, at least partly via induction of HSP72.