外源性PCr对小鼠全脑缺血性损伤的保护作用

[目的]探讨外源性磷酸肌酸(phosphocreatine,PCr)对动物急性脑缺血损伤的保护作用。[方法]雄性昆明种小鼠110只,体重20～24 g,随机分为对照组,模型组,高、低剂量PCr给药组及尼莫地平阳性对照组。采用断头法制备全脑永久性缺血模型;双侧颈总动脉反复结扎再灌法制备全脑缺血再灌注损伤模型。分别观察外源性PCr(1.0,2.0 g·kg-1,iv;1.5,4.5 g·kg-1,ip)对脑缺血后呼吸持续时间、脑含水量、脑组织SOD活力、MDA含量、CD14表达等指标变化及脑组织病理学改变的影响。[结果](1)与对照组比较,外源性PCr(4.5 g·kg-1,ip)可明显延长小鼠全脑缺血后呼吸时间(P<0.05);提高脑组织中SOD活力并降低MDA浓度(1.5,4.5 g·kg-1,ip)(P<0.05)。(2)与模型组比较,外源性PCr(1.0、2.0 g·kg-1,iv)可显著降低脑缺血再灌注后脑含水量(P<0.05);抑制CD14在脑组织内的表达(P<0.05);减轻脑组织病理学变化。[结论]脑缺血损伤早期给予外源性PCr可显著降低小鼠全脑永久缺血及缺血再灌注所致脑组织损伤,减轻脑水肿,保护脑功能。上述作用与药物提高组织抗氧化能力并降低损伤后内毒素侵袭有关。

Effects of exogenous phosphocreatine on cerebral ischemia injury in mice

[Objective]To investigate the effect of Phosphoreatine(PCr) on cerebral ischemic injury in mice.[Methods]The adult male kunming mice were randomly divided into control group,cerebral ischemia injury group,PCr treated groups(1.0,2.0 g·kg-1,iv;1.5,4.5 g·kg-1,ip).The models of permanence cerebral ischemia and cerebral ischemic reperfusion injury were made by decapitation method or bilateral ligation of common carotid arteries.The gasping time after cutting head in mice was recorded.The levels of malondialdehyde(MDA),superoxide dismutase(SOD) activities and CD14 in brain tissue were measured.Brain water content was determined by estimation of the wet/dry weight ratio.[Results](1) In the test of permanence cerebral ischemia model,the gasping time in PCr treated group(4.5 g·kg-1,ip) was significantly longer compared with the control group(P<0.05),the level of MDA in PCr treated groups(1.5,4.5 g·kg-1,ip) was significantly decreased(P<0.05),and the level of SOD activity was significantly improved(P<0.05).(2) In the tests of cerebral ischemia reperfusion model,compared with model group,the water content in brain tissue of PCr(1.0、2.0 g·kg-1,iv) treated group was markedly decreased(P<0.05).Simultaneously the expression of CD14 in brain tissue after eperfusion following brain ischemia(P<0.05) and the pathomorphology changes in brain were obviously reduced compared with the model group.[Conclusions]Exogenous PCr may significantly decrease the structure and function injury of brain due to permanence cerebral ischemia or cerebral ischemic reperfusion in mice.And the mechanisms of exogenous PCr ’s protective effect may be relationship with the raised anti-oxidative ability and resisted endotoxin invasion after the cerebral ischemic.