摘要
近来报道非竞争性NMDA受体拮抗剂美金胺 (Memantine)对缺氧缺血损伤 (HI)具有脑保护作用。在对HI新生大鼠先行进行了HSP70基因表达的研究基础上 ,对新生大鼠在HI前后对照应用美金胺 ,通过观察HSP70基因表达的变化 ,进一步从分子水平评估美金胺的脑保护效果。结果显示 ,HSP70mRNA在正常情况下仅有极微弱表达 ,HI后可引起其表达明显增加。应用美金胺后 ,其HSP70基因表达虽较正常对照组增高 ,但显著弱于HI组 ,提示美金胺的应用具有一定的脑保护作用 ,可能减轻了HI的脑损伤 ,因而使作为一种敏感的脑缺氧缺血标志的HSP70基因的表达降低。数据显示美金胺在HI前应用较之HI后应用似有更明显的脑保护效果 ,尽管统计显示其差异无显著性意义。结合已完成的脑病理研究和病理量化评分 ,初步证实美金胺作为较安全有效的NMDA受体离子通道非竞争性拮抗剂 。
In order to explore the neuroprotective effect of Memantine against hypoxic ischemic (HI) invasion, Memantine was intraperitoneally injected at a dose of 20 mg/kg in neonatal rat models either before (PRE group) or after (POST group) cerebral hypoxic ischemia (HI), and its neuroprotective effect was evaluated by detecting the change of HSP70 gene expression. The results showed that HSP70 mRNA expression decreased significantly after Memantine administration in both of PRE and POST groups compared to that of HI group. It was estimated that Memantine could probably lighten the brain damage, and HSP70 mRNA expression as a sensitive HI marker hence decrease. Linked the prior results of cerebral pathology and the quantized score of cerebral pathology, it was thereby confirmed that Memantine, an antagonist at the N methyl D aspartate receptor, has the effect of brain protection against hypoxic ischemia.
基金
国家自然科学基金资助项目!(396 70 75 8)
