谷氨酸转运体抑制剂DHK抑制脑缺血预处理的保护作用

Effect of dihydrokainate, a selective inhibitor of glutamate transporter subtype GLT-1, on the protection of cerebral ischemic preconditioning in rats

目的:观察谷氨酸转运体GLT1抑制剂二氢卡因酸盐(DHK)对脑缺血预处理(CIP)诱导脑缺血耐受的影响.方法:采用四血管闭塞法制作大鼠全脑缺血模型,右侧脑室注射DHK.脑组织切片硫堇染色法观察海马CA1区锥体神经元迟发性死亡(DND)程度,确定组织学分级.结果:假手术组和CIP组海马CA1区未见明显的DND;损伤性缺血组海马CA1区有明显的DND;CIP+损伤性缺血组海马CA1区DND不明显;DHK+CIP+损伤性缺血组中,DHK阻断了CIP对海马CA1区锥体神经元的保护作用.定量分析发现,DHK+CIP+损伤性缺血组较CIP+损伤性缺血组的保护效应明显降低.结论:DHK可抑制CIP诱导的脑缺血耐受.

AIM： To investigate the effect of dihydrokainate （DHK） on brain ischemic tolerance （BIT） induced by cerebral ischemic preconditioning （CIP）. METHODS： Cerebral ischemic model was made by four-vessel occlusion, and DHK was injected into right lateral cerebral ventricle. The brain of the rats was sectioned and stained with thionin to show delayed neuronal death （DND） in the CA1 hippocampus and identified for histological grade. RESULTS： There was no apparent DND in sham operation and CIP groups. Obvious DND was found in brain ischemic injury group, while there was no visible neuronal changes in CIP ＋ brain ischemic injury group. But DHK blocked the protection of CIP on the CA1 hippocampus. The quantitative analysis of the protective effect of CIP on the CA1 hippocampal neurons showed that the protective effect was obviously decreased. CONCLUSION： DHK can block BIT induced by CIP.