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p38MAPK在沙土鼠脑缺血再灌注海马神经元损伤中的作用 被引量:8

The role of p38MAPK in ischemia-reperfusion injury to the hippocampal neurons in gerbils
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摘要 目的 探讨p38MAPK在沙土鼠脑缺血再灌注损伤海马神经元中的作用。方法 采用沙土鼠双侧颈动脉阻断前脑缺血模型 ,随机分成假手术组 (sham组 )、缺血再灌注组 (IR组 )、对照组 (control组 )、SB2 0 2 190组及P7935 0组 ,后 3组分别侧脑室注射 1%DMSO、p38MAPK特异性抑制剂SB2 0 2 190和激动剂P7935 0。每组根据再灌注时间不同再分为 1天、3天和 5天 3个亚组 ,每亚组 6只动物。在预定时间点行开阔法行为学检查 ,显微镜下计数海马CA1、CA3区存活神经元数目 ,TUNEL法检测CA1区凋亡细胞。结果 SB2 0 2 190可以显著减少沙土鼠再灌注 3天、5天的探索活动 ,增加存活海马神经元数目 ,减少CA1区神经元的凋亡 (P <0 .0 5 ,vsIR组 ) ;而P7935 0可以显著增加沙土鼠再灌注 1天、3天、5天的探索活动 ,减少海马CA1、CA3区存活神经元数量 ,增加海马CA1区神经元的凋亡 (P <0 .0 5 ,vsIR组 )。结论 抑制p38MAPK的激活可以减轻脑缺血再灌注引起的海马神经元损伤。 Objective To study the role of p38MAPK in the hippocampal neuronal injury after cerebral ischemia-reperfusion in gerbils.Method Forebrain ischemic model induced by bilateral common carotid artery obstruction in gerbil was adopted. The gerbils were randomly divided into 5 groups: sham operation group, ischemia-reperfusion group (IR group),(vehicle) control group, SB202190 group and P79350 group. 1% dimetyl sulphoxide (DMSO), SB202190 (the specific inhabitor of p38MAPK ) and P79350 (the activator of p38MAPK) were injected into the lateral ventricle in the last three groups respectively. At different time spots after IR, with the animals designated as subgroups 1 d,3 d and 5 d (n=6 each), the animals' behavior was observed by open field method, the survival neurons of hippocampal CA1 and CA3 areas were counted on pathological sections,the apoptotic neurons were detected in CA1 area by TUNEL method.Results In SB202190 subgroups 3 d and 5 d, the behavior marks were found decreased, the survival neurons in CA1 and CA3 areas increased, and the apoptotic cells in CA1 area decreased, as compared with the corresponding IR subgroups ( P<0.05). While in the three P79350 subgroups, the behavior marks increased, the survival neurons in CA1 and CA3 areas decreased and the apoptotic cells in CA1 area increased (P<0.05).Conclusion Inhabiting the activation of p38MAPK may attenuate the hippocampal neurons ischema-reperfusion injury.
出处 《徐州医学院学报》 CAS 2004年第4期285-289,共5页 Acta Academiae Medicinae Xuzhou
基金 江苏省教育厅资助课题 (0 1KJB32 0 0 12 0 3KJB32 0 14 2 )
关键词 P38MAPK 沙土鼠 脑缺血 再灌注损伤 海马神经元 SB202190 P79350 细胞凋亡 丝裂素活化蛋白激酶 激动剂 p38MAPK SB202190 P79350 apoptosis ischemia-reperfusion injury gerbil
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参考文献5

  • 1Barone FC, Irving EA, Ray AM, et al. SB 239063, a second - generation p38 mitogen - activated protein kinase inhibitor, reduces brain injury and neurological deficits in cerebral focal ischemia[J]. JPET,2001,296(2): 212 - 321.
  • 2Zhan RZ, Wu CR, Hideyoshi F, et al. Both caspase- dependent and caspase - independent pathways may be involved in hippocampal CA1neuronal death because of loss of cytochrome c from mitochondria in a rat forebrain ischemia model[J] .J Cereb Blood Flow Meta
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