急性脑缺血大鼠海马和齿状回神经元β-NGF与NGFRs基因表达变化对其生存影响的研究  

The effect of expression variations of β-NGF and NGFRs on neuron survival in hippocam pus and den tate gyrus of acute cerebral ischemic rats

作　　者：崔瑾[1] 于士柱[1] 张天林[1] 管欣琴[1] 安同岭[1] 王虔[1] 李庆有[1] 杨露春[1] 

机构地区：[1]天津医科大学总医院,天津市神经病学研究所,300052

出　　处：《现代神经疾病杂志》2003年第3期137-141,共5页

基　　金：天津市科委重点科研项目基金资助(953105711)

摘　　要：目的探讨急性脑缺血时大鼠海马各区及齿状回神经元β-神经生长因子(β-nervegrowthfactor,β-NGF)及其受体trkA2和p75NGFR基因表达变化对神经元生存的影响。方法采用mRNA原位杂交、免疫组织化学染色和原位细胞凋亡检测等方法,分别观察各缺血组和对照组大鼠海马各区及齿状回神经元上述3种基因表达的变化和神经元凋亡状况。结果正常大鼠海马和齿状回神经元均表达β-NGF、trkA2和p75NGFRmRNA及蛋白,无神经元凋亡。急性脑缺血后,海马CA1、CA2和CA3区均出现大量凋亡的神经元,其密度均明显高于同组CA4区及齿状回(P<0.01)。缺血组海马CA1、CA2和CA3区神经元β-NGF、trkA2和p75NGFRmRNA及蛋白的表达水平均低于对照组的对应区域(P<0.05或P<0.01),它们的表达水平彼此间均呈正相关(r=0.213～0.835,P<0.05～P<0.0001),并均与对应区域的凋亡神经元密度呈负相关(r=?0.551～?0.823,P<0.0001)。缺血组CA4区及齿状回神经元β-NGF及其受体的表达无显著变化,且与凋亡无相关关系。结论β-NGF以自分泌和(或)旁分泌方式发挥神经元保护作用,β-NGF可能对其两种受体的表达具有正性诱导作用,缺血引起的β-NGF及其两种受体表达减少可能是导致对缺血敏感的海马CA1、CA2和CA3区神经元凋亡的重要因素。Objective To study the effect of expression variations ofβ-nerve growth factor(β-NGF)and its receptors(NGFRs)trkA 2 and p75 NGFR on neuronal survival in hippocampus and dentate gyrus of acute cerebral ischemic rats.Methods In situ hybridization with mRNA,immunohistochemical staining and TUNEL were performed to detect the expression variations of mRNAs and proteins ofβ-NGF,trkA 2 and p75 NGFR ,and apoptotic neurons in hippocampus and dentate gyrus in control group and cerebral ischemic rats.Results Neurons in hippocampus and dentate gyrus of normal rats had no apoptosis,but could express mR-NAs and proteins ofβ-NGF,trkA 2 and p75 NGFR .After acute ischemia,a number of apoptotic neurons were found in regions of CA1,CA2and CA3of hippocampus,and their densities were significantly higher than those in CA4region and dentate gyrus of the same group rats(P<0.01).Compared with the control rats,all of the expression levels of above mRNAs and proteins in regions of CA1,CA2and CA3of acute ischemia rats were significantly decreased(P<0.05or P<0.01)and all of the expression levels were positively correlated with one another(r=0.213-0.835,P<0.05-P<0.0001)negatively correlated with the densities of apoptotic neurons in the corresponding regions(r=?0.551-?0.823,P<0.0001).There was no significant change in neuronalβ-NFG and its receptor expression in CA4and dentate gyurs of ischemic rats.Con clu sion Theβ-NGF can play an important role in protecting neurons by an autocrine and/or paracrine manner,andβ-NGF may be positively inducing the expressions of its receptors and the decreasing expression ofβ-NGF and its re-ceptors resulted in ischemia may be the key factor of neuronal appotosis in ischemia sensitive hippocampus regions CA1,CA2and CA3.[

关 键 词：急性脑缺血 海马 齿状回神经元 Β-NGF NGFRs 基因表达 

分 类 号：R741[医药卫生—神经病学与精神病学]