| 摘要: |
| 目的研究脑缺血预处理对沙鼠前脑缺血再灌注后热休克蛋白70(HSP70)表达水平及动物学习记忆能力的影响。方法100只蒙古沙鼠随机分成假手术(Sham)组、前脑缺血再灌注(I/R)组、脑缺血预处理(IP)组,放线菌酮＋脑缺血预处理(Cycloheximide+IP)组,每组25只。后3组参照Kirino法制备前脑缺血动物模型,Kitagawa法制备脑缺血预处理动物模型。再灌注后1、2、3 d取各组动物脑组织行H-E染色,观察海马CA1区神经元形态变化；用TUNEL法检测神经细胞凋亡情况；用免疫组织化学和蛋白质印迹法检测HSP70的表达水平。再灌注后3、4、5、6、7 d用4-PTT旱路迷宫法对沙鼠的学习记忆能力进行评定,各取均值。结果与Sham组比较,I/R组沙鼠海马CA1区存活神经元密度降低(P<0.05),神经细胞凋亡数量增多(P<0.05),HSP70 表达量增加(P<0.05),学习记忆能力下降(P<0.05)；与I/R组比较,IP组中沙鼠海马CA1区存活神经元密度增加(P<0.05),凋亡神经细胞数量回降(P<0.05),HSP70 表达水平进一步增加(P<0.05),学习记忆能力得到改善(P<0.05)；而Cycloheximide+IP组基本消除了IP组中的上述改变,神经细胞形态及密度,神经细胞凋亡数量,HSP70 表达水平、学习记忆能力与I/R组相似。结论缺血预处理对脑缺血性损伤具有保护作用并可改善脑缺血后的学习记忆功能障碍。这可能是通过促进 HSP70表达增加,启动内源性的神经保护机制而加强了对再次缺血损伤的保护作用。 |
| 关键词: 缺血预处理 脑缺血 热休克蛋白70 缺血耐受 |
| DOI：10.3724/SP.J.1008.2010.055 |
| 投稿时间：2008-10-12修订日期：2009-12-10 |
| 基金项目:河北省卫生厅重点课题(07347). |
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| Effect of ischemic preconditioning on HSP70 expression and learning/memory after cerebral ischemia-reperfusion in gerbils |
| LI Jian-min1*,ZHAO Ya-ning2,AN Chao-wang1,CHEN Chang-xiang1,ZHU Jun2,FU Ai-jun1 |
| (1.Department of Neurosurgery,Affiliated Hospital of Northern China Coal Medical College,Tangshan 063000,Hebei,China;2.Department of Nursing,Northern China Coal Medical College,Tangshan 063000,Hebei,China) |
| Abstract: |
| ObjectiveTo study the effect of ischemic preconditioning on heat-shock protein 70 (HSP70) expression and the learning,memory functions after forebrain ischemia-reperfusion injury in gerbils.MethodsGerbils (n=100) were evenly randomized into four groups:Sham group,ischemia-reperfusion(I/R) group,ischemia preconditioning(IP) group,and Cycloheximide + IP group (Cycloheximide was administered 30 min before IP).Transient forebrain ischemia-reperfusion model was established by bilateral common carotid artery occlusion according to the method described previously,and ischemia preconditioning model was established as described by Kitagawa.Changes of neuron morphous in hippocampus CA1 region were observed by H-E staining 1,2,and 3 days after reperfusion.The expression of HSP70 was examined by immunohistochemistry and Western blotting assay.Neuron apoptosis was detected by TUNEL method.The learning/memory functions of gerbils were examined using 4-PTT dry path maze 3,4,5,6,and 7 days after reperfusion.ResultsCompared with Sham group,I/R group had significantly decreased survival neurons(P<0.05),increased neuron apoptosis(P<0.05),increased expression of HSP70 (P<0.05),and decreased learning/memory functions(P<0.05).Compared with I/R group,IP group had significantly increased survival neurons(P<0.05),decreased neuron apoptosis (P<0.05),and increased expression of HSP70 (P<0.05),and improved learning/memory functions(P<0.05).However,cycloheximide almost totally abolished the effect of ischemia preconditioning,with the neuron morphology,density,apoptosis,HSP70 expression,and learning/memory functions similar to those of I/R group.ConclusionIschemic preconditioning can protect against cerebral ischemia injury and improve the learning/memory functions after forebrain ischemia-reperfusion damage,which is possibly through promoting HSP70 expression and starting endogenous neuroprotective mechanism,subsequently reinforcing the protective effect against ischemia. |
| Key words: ischemia preconditioning cerebral ischemia heat-shock protein 70 ischemic tolerance |
