摘要
目的 研究亚低温对前脑缺血再灌注损伤沙土鼠海马磷酸化胞外信号调节激酶（p-ERK）及磷酸化c-Jun氨基末端蛋白激酶（p-JNK）水平的影响。方法 蒙古沙土鼠120只，随机分为4组（n=30）：常温假手术组（SH组）、常温缺血再灌注组（IR组）、低温假手术组（HSH组）、常温缺血低温再灌注组（HIR组）。腹腔注射1％戊巴比妥钠40mg／kg麻醉后，分离出双侧颈总动脉，IR组、HIR组分别夹闭双侧颈总动脉，5min后恢复脑血流灌注，IR组再灌注时维持正常体温（36．5—37．5℃），HIR组再灌注即刻开始降温，10min内降至32．5—33．5℃，并维持4h；SH组、HSH组只分离双侧颈总动脉不夹闭，SH组维持正常体温，HSH组分离双侧颈总动脉后5min开始降温，10min内降至32．5—33．5℃，并维持4h。每组于再灌注2h,4h、1d、3d、5d分别随机取6只动物，采用开阔法观察沙土鼠的行为学，行为学观察完毕立即处死大鼠，取脑组织，采用TUNEL法检测海马CA1区、CA3区细胞凋亡情况，免疫组化法测定海马CA1区、CA3区、DG区p-ERK、p-JNK的水平。结果HIR组再灌注1—5d沙土鼠行为学异常及海马凋亡细胞计数较IR组降低（P〈0．01）；与SH组或HSH组比较，IR组及HIR组再灌注期间海马CA3区及DG区p-ERK水平增加（P〈0．05），但IR组与HIR组比较差异无统计学意义；4组海马CA1区均无p-ERK表达。与sH组比较，IR组再灌注2h-5d海马CA1区、CA3区p-JNK水平增加，且HIR组再灌注2h-1d海马CA1区、CA3区p-JNK水平低于IR组（P〈0．05）。结论 亚低温（32．5-33．5℃）4h可减轻沙土鼠脑缺血再灌注损伤，其机制与抑制再灌注早期p-JNK的激活有关，而与p-ERK水平无关。
Objective To investigate the effects of mild hypothermia on the p-ERK and p-JNK expressin in hippocampus after forebrain ischemia-reperfusion （I/R） in gerbils. Methods One-hundred and twenty gerbils of both sexes weighing 50-80 g were randomly divided into 4 groups （ n = 30 each） ： group A normothermic sham operation （SH）; group B normothermic I/R （I/R）; group C hypothermic sham operation （HSH） and group D normothermic forebrain ischemia ＋ hypothermic reperfusion （ HI/R）. Forebrain ischemia was produced by occlusion of bilateral common carotid arteries for 5 min. Brain ischemia was confirmed by isoelectricity on EEG. In sham operation groups （group A and C） bilateral common carotid arteries were exposed but not occluded. In group D （HI/R） the animals were first subjected to 5 mln brain ischemia at normal body temperature （36.5-37.5 ℃ ） which was reduced to 32.5-33.5℃ within 10 rain as soon as reperfusion was started. Mild hypothermia was maintained for 4 h. Open field test was performed to evaluate the behavioral deficit at 1, 3 and 5 days after ischemia. The animals were killed at 2 h, 4 h, 1 d, 3 d and 5 d after ischemia （ n = 6 each）. The brains were immediately removed for detection of apoptosis （TUNEL）, determination of p-ERK and p-JNK expression （immuno-histochemistry） in hippocampal CA1, CA3 and DG regions and microscopic examination. Results The behavioral deficit and the number of apoptotic neurons in hippocampus were significantly decreased in group D （HI/R） than in group B （I/R）. There was no p-ERK expression in the CA1 region in all 4 groups, p-ERK expression in CA3 and DG regions was significantly upregulated during reperfusion in group I/R and HI/R but there was no difference between the 2 groups, p-JNK expression in CA1 and CA3 regions was significantly increased in group B and D but was significantly lower in group D than in group B. Conclusion Mild hypothermia can protect the brain from I/R injury through the inhibition of the activation of p-JNK.
出处
《中华麻醉学杂志》
CAS
CSCD
北大核心
2007年第2期144-148,共5页
Chinese Journal of Anesthesiology
基金
江苏省教育厅资助课题（01KJB320012
03KJB320142）
江苏省高校自然科学研究项目（04KJB320146）
