摘要
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
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.
出处
《中国药理学与毒理学杂志》
CAS
CSCD
北大核心
2001年第6期418-422,共5页
Chinese Journal of Pharmacology and Toxicology
