摘要
目的通过动态观察亚低温(33℃,4h)对沙土鼠前脑缺血/再灌注后不同时间点海马CA1区Bcl-2、Caspase-3的表达及凋亡细胞的影响,探讨亚低温脑保护的可能机制。方法采用沙土鼠双侧颈总动脉阻断5min前脑缺血/再灌注损伤模型,随机分为假手术组,常温再灌注组,低温假手术组,低温再灌注组,每组根据再灌注的不同时间点(2h、4h、1d、3d、5d)又分为5个对应的亚组(n=6)。在预定时间点行开阔法迷宫检查,TUNEL法检测海马CA1区的凋亡细胞,HE染色检测海马存活细胞,免疫组化检测Bcl-2、Caspase-3在海马各区的动态变化。结果4h亚低温可减少缺血沙土鼠1、3、5d的探索活动及CA1区的凋亡细胞,增加存活细胞,明显抑制脑缺血后海马CA1区Caspase-3早期的表达(2、4h),但对Bcl-2的表达没有影响。结论4h亚低温对沙土鼠5min前脑缺血有确切的保护作用,对Bcl-2的表达没有影响,抑制海马CA1区缺血/再灌注早期Caspase-3的激活可能是其减少海马细胞凋亡,产生脑保护作用的机制之一。
Aim To investigate the effect of mild hypothermia on levels of Bcl-2, Caspase-3 and apoptotic neurons in hippocampus after forebrain ischemia at the different spots in gerbils. Methods Forebrain ischemic model induced by bilateral common carotid artery obstruction was adopted. Gerbils were randomly divided into 4 groups ： sham group （SH） ： sham operation group having the same surgical procedures without bilateral carotid arteries occlusion; normothermic ischemic reperfusion （IR）： having a 5 min ischemia; hypothermia sham （HSH） ： having the same operation as SH and cooling body temperatures at 33℃±0. 5℃ for 4 h; hypothermic ischemic reperfusion （HIR） ： having a 5 min ischemia and immediately after reperfusion cooling body temperatures at 33℃±0. 5℃ for 4 h. At different time spots after ischemia, with animals desig- nated as subgroups 2,4 h, 1,3 d and 5 d （n =6 in each）. The animals behavior was observed by open field method. The apoptotic neurons were detected in CA1 area by TUNEL method. The survival neurons of hippocampal CA1 regions were accounted on HE staining slides. Expressions of Bcl-2 and Caspase-3 in hippocampal CA1 area were detected by SP immunocytochemical technique. Results The behavioral marks and the number of apoptotic neuons in hippocampal CA1 region were much less in HIR group than those in IR. The number of survival neurons in hippocampal CA1 regions in HIR group was more than that in IR group. The expression of Caspase-3 was reduced in the CA1 area in HIR group than that in IR group at early reperfusion （2 h and 4 h） , but Bcl-2 expression did not alter. Conclusions Hypothermia can significantly protect neurons against cerebral ischemia, and its protective mechanism contains reducing Caspase-3 activation at early reperfusion, but does not alter Bcl-2 expression.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2007年第1期77-81,共5页
Chinese Pharmacological Bulletin
基金
江苏省教育厅资助课题(No01KJB320012
03KJB320124)
江苏省高校自然科学研究项目(No04KJB320146)
