摘要
目的通过研究亚低温对大鼠局灶性脑缺血再灌注后基质金属蛋白酶-9(MMP-9)表达和细胞凋亡的影响,探讨亚低温脑保护的可能机制。方法将雄性SD大鼠39只分为假手术组、常温缺血组和缺血期亚低温组。制作大脑中动脉阻塞(MCAO)模型,缺血2h再灌注48h,HE染色观察各组大鼠脑组织形态学改变;采用TTC染色法观察梗死体积;TUNEL法检测细胞凋亡;免疫组化法检测MMP-9表达。结果亚低温减轻脑缺血组织病理学损伤,明显缩小脑梗死体积(P<0.05)。常温下缺血侧脑组织可见大量TUNEL阳性细胞和MMP-9免疫阳性细胞,主要位于皮质缺血半暗带区。亚低温减少脑缺血后TUNEL阳性细胞数目(P<0.05),明显下调MMP-9蛋白表达(P<0.05)。结论亚低温可能通过下调脑缺血再灌注后MMP-9表达,抑制细胞凋亡,从而发挥确实的脑保护作用。
Objective To explore the neuroprotective mechanism of mild hypothermia by studying the effect of mild hypothermia on the matrix metalloproteinase-9 (MMP-9) expression and apoptosis following focal cerebral ischemia-reperfusion in rats. Methods 39 male Sprague-Dawley rats were randomly divided into sham-operated group, normal temperature group and mild hypothermia group. The model of focal cerebral ischemia was made by middle cerebral artery occlusion (MCAO) method. After 2h of MCAO following 48h of reperfusion,the rats were decapitated and brain tissue was collected. The histological morphological damage was investigated by hematoxylin-eosin (HE) staining. The infarction volume was investigated by 2,3,5-Triphenyl tetrazolium chloride (TIC) coloring. The Apoptosis was detected by in situ end-labeling of fragmented DNA. The expression of matrix MMP-9 in brain tissue was observed by immunohistochemistry. Results Mild hypothermia significantly ameliorated the histopathological damage in ischemic brain and reduced the infarct size. 48 hours after reperfusion,TUNEL-positive and MMP-9 immunoreactivity cells were dominantly in the ischemic penumbra of the cortex in normthermic group. Whereas mild hypothermia significantly suppressed apoptosis and down-regulated MMP-9 expression. Conclusion It is hypothesized that mild hypothermia would inhibit the apoptosis by down-regulation of MMP-9 expression and then attenuate brain damage.
出处
《中风与神经疾病杂志》
CAS
CSCD
北大核心
2008年第4期414-416,共3页
Journal of Apoplexy and Nervous Diseases
基金
福建省教育厅科技项目(JB06256)
福建医科大学教授学术发展基金(JS06050)
关键词
亚低温
脑缺血再灌注
基质金属蛋白酶-9
细胞凋亡
Mild hypothermia
Cerebral ischemia-reperfusion
Matrix metalloproteinase-9
Apoptosis