Mrsić-Pelcić Jasenka, Zupan Gordana, Maysinger Dusica, Pelcić Goran, Vitezić Dinko, Simonić Ante
Department of Pharmacology, School of Medicine, University of Rijeka, Brace Branchetta 20/1, 51000 Rijeka, Croatia.
Prog Neuropsychopharmacol Biol Psychiatry. 2002 Dec;26(7-8):1319-26. doi: 10.1016/s0278-5846(02)00296-8.
The influence of 20 min global cerebral ischemia on the free arachidonic acid (FAA) level and Na+,K+-ATPase activity in the rat hippocampus at different time points after ischemia was examined. In addition, the effect of MK-801 on mentioned parameters was studied. Animals were exposed to 20 min global cerebral ischemia and were sacrificed immediately, 0.5, 1, 2, 6, 24, 48, 72, and 168 h after ischemic procedure. The level of the FAA and the Na+,K+-ATPase activity was measured during all reperfusion periods examined. Various doses of MK-801 (0.3, 1.0, 3.0, and 5.0 mg/kg) had been injected 30 min before ischemic procedure started. It was found that 20 min global cerebral ischemia induces a statistically significant increase of the FAA level immediately after ischemia and during the first 0.5 h of reperfusion. After a transient decrease, the level of FAA level increased again after 24 and 168 h of recirculation. Treatment with 3.0 mg/kg of MK-801 significantly prevented the FAA accumulation immediately and 0.5 h after ischemic insult while application of 5.0 mg/kg of MK-801 exerted a protective effect during the first 24 h. Global cerebral ischemia induces the significant decline in the Na+,K+-ATPase activity in the hippocampus starting from 1 to 168 h of reperfusion. Maximal inhibition was obtained 24 h after the ischemic damage. Application of 3.0 mg/kg of MK-801 exerted statistically significant protection during the first 24 h while the treatment with 5.0 mg/kg of MK-801 prevented fall in enzymatic activity during all reperfusion periods examined. Our results suggest that, in spite of different and complex pathophysiological mechanisms involved in the increase of FAA level and the decrease of the Na+,K+-ATPase activity, blockade of NMDA receptor subtype provides a very important strategy for the treatment of the postischemic excitotoxicity.
研究了20分钟全脑缺血对大鼠海马在缺血后不同时间点游离花生四烯酸（FAA）水平和Na +，K + -ATP酶活性的影响。此外，还研究了MK-801对上述参数的作用。动物经历20分钟全脑缺血，并在缺血操作后立即、0.5、1、2、6、24、48、72和168小时处死。在所有检查的再灌注期测量FAA水平和Na +，K + -ATP酶活性。在缺血操作开始前30分钟注射不同剂量的MK-801（0.3、1.0、3.0和5.0mg/kg）。结果发现，20分钟全脑缺血在缺血后立即和再灌注的最初0.5小时内导致FAA水平有统计学意义的升高。短暂下降后，再循环24和168小时后FAA水平再次升高。3.0mg/kg的MK-801治疗在缺血损伤后立即和0.5小时显著预防了FAA积累，而5.0mg/kg的MK-801应用在最初24小时内发挥了保护作用。全脑缺血从再灌注1至168小时开始导致海马中Na +，K + -ATP酶活性显著下降。缺血损伤后24小时获得最大抑制。3.0mg/kg的MK-801应用在最初24小时内发挥了统计学意义的保护作用，而5.0mg/kg的MK-801治疗在所有检查的再灌注期预防了酶活性下降。我们的结果表明，尽管FAA水平升高和Na +，K + -ATP酶活性降低涉及不同和复杂的病理生理机制，但NMDA受体亚型的阻断为缺血后兴奋性毒性的治疗提供了非常重要的策略。
