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神经元凋亡细胞及磷酸化p38表达的影响,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、d1、3、d5)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CA1/3区的凋亡细胞,免疫组化检测pp38在海马各区的动态变化。结果4h亚低温可显著减少缺血沙土鼠d1、d3、d5的探索活动及CA1/区的凋亡细胞,明显抑制脑缺血后海马CA1区pp38早期的表达(2h、4h)。结论4h亚低温治疗对沙土鼠5min前脑缺血有明确的保护作用,抑制海马CA1区缺血再灌注早期pp38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 the phosphorylation levels of p38 and apoptotie neurous in hippoeampus in gerbils after forebrain isehemia at the different time. Method： Forebrain isehemie model indueed by bilateral eommon earotid artery obstruetion in gerbil was adopted. The gerbils were randomly divided into 4 group： SH： sham operation group having the same surgieal proeedures without bilateral carotid arteries occlusion. IR： having a 5 min ischemia. HSH： having a operates as SH and cooling body temperatures of 33℃ ± 0.5℃ for 4 h. HIR： having a 5 min ischemia and immediately after reperfusion cooling body temperatures of 33℃ ± 0. 5℃ for 4 h. At different time spots after ischemia, with the animals designated as subgroups 2 h ,4 h ,d 1 ,d 3 ,d 5 （n = 6 each）. The animals behavior was observed by open field method . The apoptotic neurons were detected in CA1/CA3 area by TUNEL methed. The expression of p-p38 in hippocampal CA1/CA3 area was detected by SP immunocytochemical technique. Results the behavioral mark and the number of apoptosis neuous in hippocampal CA1/CA3 region were much less in HIR than in IR. The expression of p- p38 was reduced in the CA1 area in HIR group at early time points （2 h,4 h）. Conclusion Hypothermia can significantly pro- tect neurons against cerebral ischemia and reducing the p38 kinase activation at the early time may be one of the protective mechanisms.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2005年第8期970-973,共4页
Chinese Pharmacological Bulletin
基金
江苏省教育厅资助项目(No01KJB320012
03KJB320124)
