亚低温对大鼠全脑缺血再灌注损伤后海马CA_1区c-Jun蛋白表达的影响  

Mild hypothermia affects c-Jun expression in hippocampal CA_1 subfield following globle cerebral ischemia

作　　者：王兰琴[1] 魏秀娥[1] 韩立秀 董瑞国[3] 

机构地区：[1]徐州医学院第二附属医院神经内科,江苏徐州221006 [2]枣庄市第一人民医院,山东枣庄277000 [3]徐州医学院附属医院神经内科,江苏徐州221002

出　　处：《中风与神经疾病杂志》2012年第3期209-212,共4页Journal of Apoplexy and Nervous Diseases

摘　　要：目的研究亚低温对大鼠全脑缺血再灌注损伤后海马CA1区神经元的保护作用,并探讨其可能的机制。方法采用四血管阻断法建立大鼠全脑缺血模型。SD大鼠,随机分为假手术组(SH组)、常温组(IR组)和亚低温组(HIR组)。各组在全脑缺血15min后分别再灌注6h、12h、1d、3d,采用苏木素-伊红(HE)染色观察各时间点海马CA1区细胞形态学变化和TUNEL法检测海马CA1区神经元凋亡,免疫印迹检测c-Jun蛋白表达。结果(1)HE染色结果 IR组和HIR组于全脑缺血再灌注后6h,HE染色未见明显改变,IR组缺血再灌注1d时CA1区出现严重改变,3d时损伤最严重,出现细胞数目减少,细胞胞体缩小、胞核固缩深染,损伤严重,排列紊乱,核膜不清,核仁消失。而HIR组海马存活的锥体细胞数较之IR组12h、1d、3d时间点均明显增加(P<0.05)。(2)TUNEL标记IR组于缺血再灌注后6h在海马CA1区阳性细胞开始增多,缺血再灌注1 d时阳性细胞数最多。而HIR组各时间点阳性细胞数均较IR组明显减少(P<0.01)。(3)免疫印迹结果全脑缺血再灌注后6h c-Jun蛋白在IR组海马CA1区表达开始增加,12h达高峰,持续到3d;HIR组在各时间点的表达均弱于IR组(P<0.01)。结论亚低温通过减少海马CA1区c-Jun的表达,抑制海马CA1区神经元的凋亡,可能是亚低温脑保护作用的机制之一。Objective To investigate the neuroprotection of mild hypothermia on the hippocampal CA1 neurons following global cerebral isehemia/reperfusion in SD rat models, and to explore the possible underlying mechanism. Methods Global cerebral ischemia/reperfusion model was produced by 4-VO method. Rats were randomly divided into 3 groups： sham （ SH ） group, normothermie ischemie reperfusion （IR） group and hypothermie ischemie reperfusion （HIR） group. 15 rain after the cerebral ischemia, the reperfusion was performed for 6h, 12h, 1 d and 3d. The changes of hippocampal neurons morphology in the CA1 subfield were observed by hematoxylin-eosin （ HE ） staining and the neuron apoptosis was detected by TUNEL method. The c-Jun expression was detected by immuno-blotting test at each time point. Results Neurons in hippocampal CA1 subfield of IR group were observed abnormal appearance by HE staining with pyknotie nucleus, shrunken shape and destroyed-former lines on ld after isehemia/reperfusion, especially on 3d after isehemia/reperfusion. Compared with IR group,the number of normal cells increased in hippocampal CA1 subfield of HIR group at 12h, ld and 3d （P 〈 0.05 ）. Compared with SH group, markedly TUNEL positive cell increased in hippocampal CA1 subfield of IR group at 6h, especially on ld（ P 〈 0.01 ）. The number of apoptotic cells in hippocampal CA1 subfield of HIR group were less than that of IR group at corresponding time（ P 〈 0.01 ）. In CAm subfield of IR group after global cerebral isehemia/ reperfusion, c-Jun peaked at 12h and continued until 3d,and the espression of c-Jun significantly decreased in hippocampal CA1 subfield of HIR group at corresponding time（P 〈 0.01 ）. Conclusion Mild hypothermia decreases number of apoptotic cells in hippocampal CA1 subfield by inhibiting the overexpression of c-Jun and protect neurons.

关 键 词：全脑缺血 亚低温 C-JUN 凋亡 

分 类 号：R743[医药卫生—神经病学与精神病学]