NMDA受体拮抗剂MK-801对缺氧缺血性脑损伤保护作用的机制探讨(英文)

目的　NMDA型谷氨酸受体的激活在缺氧缺血性脑损伤 (HIBD)的病理生理过程中具有重要的作用。该研究探讨NMDA型谷氨酸受体拮抗剂MK 80 1对HIBD的保护机制。方法　 30只 7日龄SD大鼠随机分为正常对照组、HIBD组和HIBD +MK 80 1组 ,每组 1 0只 ,后两组大鼠结扎右颈总动脉后暴露于低氧环境制备HIBD模型 ,HIBD +MK 80 1组大鼠于低氧处理前腹腔注射MK 80 1 0 .3mg/kg。所有大鼠于HI后立即断头处死 ,制备脑单细胞悬液 ,以流式细胞仪测定脑细胞线粒体跨膜电势 (△Ψm)、以荧光扫描仪测定脑细胞内游离钙(Ca2 + ]i)水平。结果　与正常对照组相比 ,HIBD组大鼠双侧脑细胞△Ψm值及右 :左△Ψm比值均显著降低 ,Ca2 + ]i显著升高 ,差异均有显著性 (P <0 .0 5或 0 .0 1 ) ;MK 80 1 +HIBD组大鼠脑细胞右 :左侧△Ψm比值较HIBD组升高 ,其差异有显著性 (P <0 .0 5 ) ,但两组间脑细胞右 :左 Ca2 + ]i的比值无显著性差异 (P >0 .0 5 )。结论　MK 80 1对缺氧缺血性脑损伤的保护作用与其改善脑细胞线粒体功能有关 ,而与其对 Ca2 + ]i水平的影响关系不大 ,其保护机制可能不是经过“NMDA受体 Ca2 + ]i △Ψm”途径、而是通过“NMDA受体 其它 △Ψm”途经发挥作用。

Mechanisms of the protective effect of MK2801 against hypoxic-ischemic brain damage

Objective The activation of NMDA receptor plays an important role in the pathophysiological process of hypoxic-ischemic brain damage (HIBD). This paper aims at studying the mechanism of the protective effect of NMDA receptor antagonist MK-801 against HIBD. Methods Thirty 7-day-old SD rats were randomly assigned into Normal control, HIBD and HIBD+ MK-801 groups (n= 10 each). The rots in the latter two groups were kept in an enviroment of 8% O2 after their right common carotid arteries were ligated. The rats in the HIBD+ MK-801 group were injected with 0.3 mg/kg of MK-801 intraperitoneally before hypoxia exposure. All rots were sacrificed by decapitation immediately hypoxia and ischemia (HI). The single cell suspension of each hemisphere was prepared and the mitochondrial membrane potential (△ψm) and intracellular free calcium (Ca2+ ]i) of the brain cell suspension were measured by flow cytometry and fluorescence spectrophometer respectively. Results Compared to the Normal control group, the△ψm levels of both hermispheres and the right to left△ψm ratio in the HIBD group decreased significantly and the Ca2 +]i level increased significantly ( P ＜ 0.05 or 0.01); compared to the HIBD group, the △ψm level and the right-to-left△ψm ratio in the HIBD + MK-801 group increased significantly ( P ＜ 0.05 or 0.01 ). There was no difference in the right-to-left Ca2+ ]i ratio between the HIBD and the HIBD+ MK-801 groups. Conclusions MK-801may protect the neonatal brain from hypoxic-ischemic damage by improving the brain cell mitochondrial function through the "NMDA receptor-other-△ψm" pathway, but not through the "NMDA receptor-Ca2+ ]i-△ψ m" pathway.