MK-801对大鼠局灶性脑缺血损伤时的脑保护作用

Protective effects of MK-801 on ischemic in injury size, blood-brain barrier breakdown, and edema formatin in focal cerebral ischemia

目的：在大脑中动脉闭塞后，血脑屏障通透性的改变，脑水肿和脑梗塞是最常见的病理变化。本实验观察了MK－801（dizocilpine，一种高效非竞争性NMDA受体拮抗剂）在大鼠大脑中动脉闭塞时的脑保护作用。方法：用插线法制作局灶性脑缺血模型后，测定血脑屏障通透性，脑含水量，缺血损伤面积和体积。结果：缺血组梗塞侧皮质EB含量为：（8．82±1．35）μgweiht，在缺血前30min加入MK－801组梗塞侧皮质伊文思蓝（EB）含量下降为：（5．14±1．20）μg／gweight（P＜0．01），在缺血后30min加入MK－801组梗塞侧皮质EB含量下降为：（6．44±1．09）μg／gweight（P＜0.05）；缺血组梗塞侧脑含水量为：（80．29±2．44）％，在缺血前对30min加入MK－801组梗塞侧脑含水量下降为：（75．62±1．84）％（P＜0．01），在缺血后30min加入MK-801组梗塞侧脑含水量下降为：（76．39±2．20）％（P＜0．01）；缺血组梗塞体积为：（495.75±55．91）mm3，在缺血前30min加入MK-801组梗塞体积下降为：（180．65±9．67）mm3（P＜0．01），在缺血后则30min加入MK-801组梗塞体积下降为：（316.08±．93）mm3（P＜0．05）。结论：MK-801不仅可防止脑梗塞体积扩大，还可改善血脑屏障通透性和降低脑水肿，而具有脑保护作用。

AIM: Blood- brain barrier(BBB) permeability alteration, brain edema, and cerebral infarction are general pathological changs after middle cerebral artery occlusion (MCAO). The purpose of present study was to evaluate the effectiveness of MK - 801 (dizocipine), an potent and non - competitive N - methyl - D - aspartate receptor antagonist METHODS: The model of focal cerebral ischemia was established in rats by reversible inserting a nylon thread with a diameter of 0.2 mm into the anterior cerebral artery through the internal carotid artery, we measured ischemic injury size and volume, brain edema, and BBB permeability to Evans blue. RESULTS: The Evans blue content in the cortex of the MK - 801 -treated group significantly reduced from ischemic group of (8. 82 ±1. 35 ) μg' g-1 weight to MK - 801 - treated groups of (5. 14 ±1 .20)μg.g-1 weight (P < 0.01) in pre - treated, and of (6.44±1 .09) μg.g-1 weight (P < 0. 05) in post - treated. The cerebral water content was significantly elevated from a value of (74. 97± 2. 34) % in the contralateral hemisphere to (80. 29 ± 2. 44) %, in the ischemic hemisphere. In the MK - 801 -treated groups, water content significantly reduced from ischemic group of (80.29± 2.44) % to MK - 801 - treated grops of (75 .62±1 .84) % (P < 0. 01) in pre - treated, and (76.39± 2.20) % (P < 0. 01 ) in post - treated. Cerebral infarction was significantly reduced in the MK - 801 - treated animals from a value of (495 .75±55. 91) mm3 in the ischemic hemisphere to MK - 801- treated groups of (180.65±9.61 )mm3(P < 0. 01) in pre - treated, and of (316. 08±68. 93)mm3 (P < 0. 01 ) in post - treated. CONCLUSION: MK -801, which decreased infartion volume, and BBB permeability, attenuated ischemic brain edema significantly, has protective effect to brain.