脑缺血再灌流大鼠脑胶质源性神经营养因子基因表达的变化

探讨脑缺血再灌流不同时程及不同程度缺血对海马及皮层胶质源性神经营养因子（ｇｌｉａｌｃｅｌｌｌｉｎｅ ｄｅｒｉｖｅｄ ｎｅｕｒｏｔｒｏｐｈｉｃ ｆａｃｔｏｒ， ＧＤＮＦ）基因表达的影响，以及Ｎ甲基Ｄ天冬氨酸（Ｎｍ ｅｔｈｙｌＤｓａｐａｒｔａｔｅ， ＮＭＤＡ）受体拮抗剂，钙离子通道阻断剂是否能调节缺血病态下ＧＤＮＦｍ ＲＮＡ的表达。参照Ｓｍ ｉｔｈ 等方法建立大鼠前脑缺血再灌流动物模型。用ＤＩＧＯｌｉｇｏｎｕｃｌｅｏｔｉｄｅ ３′ｅｎｄ ｌａｂｅｌｉｎｇ Ｋｉｔ，标记５１ ｍ ｅｒ的ＧＤＮＦ寡核苷酸探针在含有海马结构的冰冻组织切片上进行原位杂交检测ＧＤＮＦｍ ＲＮＡ的表达。１０ ｍ ｉｎ 缺血再灌流２ ｈ，齿状回ＧＤＮＦｍ ＲＮＡ表达上调。再灌流６ ｈ，ＣＡ１，ＣＡ３ 和皮层ＰＡＲ区ＧＤＮＦｍ ＲＮＡ表达亦见增多，２４ ｈ 达高峰。Ｋｅｔａｍ ｉｎｅ 可使ＧＤＮＦ的基因表达在海马结构及皮层ＰＡＲ区明显低于相应的缺血再灌流组，统计学差异显著（Ｐ＜ ００５）。脑缺血再灌流时ＧＤＮＦ基因表达增加，对缺血神经元可能起保护作用。Ｋｅｔａｍ ｉｎｅ可阻断缺血后ＧＤＮＦｍ ＲＮＡ 的表达增加，提示ＮＭＤＡ谷氨酸受体很可能参与介导了缺

CHANGES OF GDNF mRNA EXPRESSION IN RAT BRAIN FOLLOWING CEREBRAL ISCHEMIA REPERFUSION

The effect of ischemia reperfusion on the expression of GDNF mRNA in the hippocampus and cortex in rat brain was observed and the NMDA receptor antagonist and Ca 2 channel blocker were used for studying whether they regulate the expression of GDNF mRNA under the condition of cerebral ischemia. A transient forebrain ischemia and reperfusion model was established in rat according to Smith et al method. The expression of GDNF mRNA was examined by in situ hybridization using oligonucleotides probe for GDNF mRNA in samples of rat brain. The expression of GDNF mRNA was increased in the dentate gyrus at 2 h after 10 min ischemic insult, in hippocampus CA1, CA3 and cortical PAR region at 6 h. The maximum expression of GDNF mRNA was found at 24 h following reperfusion. The increase of GDNF mRNA expression induced by ischemia was reversed by treatment with ketamine. After transient ischemia the expression of GDNF mRNA was increased and probably prevented the neurons from ischemic injury. Up regulation of GDNF mRNA expression after ischemia may be mediated by NMDA glutamate receptor.