van der Weerd Louise, Lythgoe Mark F, Badin Romina Aron, Valentim Lauren M, Akbar Mohammed Tariq, de Belleroche Jackie S, Latchman David S, Gadian David G
RCS Unit of Biophysics, Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK.
Exp Neurol. 2005 Sep;195(1):257-66. doi: 10.1016/j.expneurol.2005.05.002.
Heat shock proteins (HSPs) have been reported to increase cell survival in response to a wide range of cellular challenges. However, the role of HSP70 overexpression is still a matter of debate, with some reports showing protection and others not. In order to resolve these discrepancies and further investigate the action of these proteins in vivo, transgenic mice overexpressing HSP70 have been compared to wild-type mice in a middle cerebral artery occlusion model of permanent cerebral ischaemia. Previously, the effect of HSP70 was assessed histologically postmortem. In this report, magnetic resonance imaging (MRI) was used to assess the mice in vivo after the onset of stroke. The lesion volume, as measured at 24 h using T(2)-weighted MRI, was significantly smaller in HSP70 transgenic mice compared with wild-type mice. The smaller lesion size in HSP70 transgenic mice could not be attributed to differences in vascular anatomy or in cerebral blood flow during occlusion. Additionally, the apparent diffusion coefficient showed different spatial and temporal patterns between the groups, suggesting that the damage within the lesion may be less severe for HSP70 transgenic mice. Thus, we conclude that overexpression of HSP70 reduces the overall lesion size and may also limit the tissue damage within the lesion.
据报道,热休克蛋白(HSPs)可提高细胞在应对多种细胞挑战时的存活率。然而,HSP70过表达的作用仍存在争议,一些报告显示其具有保护作用,而另一些则不然。为了解决这些差异并进一步研究这些蛋白质在体内的作用,在永久性脑缺血的大脑中动脉闭塞模型中,将过表达HSP70的转基因小鼠与野生型小鼠进行了比较。此前,HSP70的作用是在死后通过组织学评估的。在本报告中,使用磁共振成像(MRI)在中风发作后对小鼠进行体内评估。使用T(2)加权MRI在24小时测量的病变体积,HSP70转基因小鼠明显小于野生型小鼠。HSP70转基因小鼠较小的病变大小不能归因于血管解剖结构或闭塞期间脑血流量的差异。此外,表观扩散系数在两组之间显示出不同的空间和时间模式,这表明HSP70转基因小鼠病变内的损伤可能较轻。因此,我们得出结论,HSP70的过表达可减小总体病变大小,也可能限制病变内的组织损伤。