褪黑素对大鼠全脑缺血-再灌注损伤及P53蛋白表达的影响

探讨了褪黑素 (MT)神经保护作用的机理 .采用大鼠“四动脉结扎法”制成全脑缺血 (2 0min) 再灌注模型 .①于再灌注开始时ipMT 2 .5或 10mg·kg- 1,于再灌注 1h断头取脑 ,检测谷胱甘肽过氧化物酶 (GSH Px) ,超氧化物歧化酶 (SOD)的活性以及丙二醛 (MDA)的含量 ;②于再灌注后 0 ,1,2 ,6h重复ipMT 2 .5或 10mg·kg- 1共 4次 ,再灌后 2 4h取脑组织 ,应用免疫组化方法检测海马CA1区神经细胞内P5 3蛋白的表达 .结果可见 ,MT两个剂量均可提高大鼠全脑缺血 再灌注后脑组织中GSH Px及SOD的活性 ,降低MDA含量 ,均可抑制海马CA1区损伤蛋白P5 3的表达 .结果表明 ,MT对缺血 再灌注后脑损伤的保护作用至少与以下两方面有关 :①增强抗氧化酶GSH Px ,SOD的活性 ,减少脂质过氧化损伤 ;②抑制缺血 再灌后P5 3蛋白的表达

Effects of melatonin on oxidization injury and on expression of P53 protein during ischemia-reperfusion in brain tissue of rats

The aim of this paper is to figure out the mechanism of the neuro- protection effect of melatonin(MT) in the global cerebral ischemia- reperfusion rats. After four-vessel occlusion(20 min), rats with global cerebral ischemia were divided into groups. ①MT 2.5 or 10 mg·kg^-1 was injected ip at the beginning of reperfusion. After 60- min reperfusion rats were sacrificed and brains were taken out to determine the activities of glutathione peroxidase(GSH-Px) and superoxide dismutase(SOD), and the content of malondialdehyde(MDA). ②Another groups of rats were injected ip with MT 2.5 or 10 mg· kg^-1 repeatedly at 0, 1, 2 and 6 h after the commence of reperfusion. Brain tissues were taken at 24 h after reperfusion and the expressions of P53 protein in neurons of hippocampal CA1 were measured by immunohistochemistry method. The results showed that both MT 2.5 and 10 mg·kg^-1 increased the activities of antioxidant enzymes such as GSH- Px and SOD, and also reduced the content of MDA in brain tissues at 1- h reperfusion after 20-min global cerebral ischemia. Both of the dosages decreased P53 immuno- reactivity in neurons of hippocampal CA1 at the end of 24 h reperfusion. The results suggest that the protection of MT on brain against cerebral injury during ischemia-reperfusion be oweing to at least two mechanisms, ①increasing activities of antioxidant enzymes SOD and GSH- Px, reducing injury induced by lipid peroxidation, and ②inhibiting the expression of P53 protein.