Pre-ischemic Administeration of L-NAME Abrogates the Protection of Simvastatin Against Ischemic/Reperfusion Injury in Rats / 中国医师杂志

ABSTRACT

Objective To investigate the effects of pre-ischemic administration of L-NAME on brain protective effects of simvastatin against focal cerebral ischemic/reperfusion injury in rats. Methods ① Animals were subjected to transient 2-hour middle cerebral artery occlusion(MCAO)with the use of the intraluminal filament method previously described by Zea Longa. ② 54 male rats were treated with simvastatin or vehicle by gavage two weeks before MCAO, and L-NAME was injected into laterar ventricle of rats 45 minutes before MCAO. After neurological deficit was assessed at 22 hours of reperfusion, rats were killed, and the brains were rapidly removed. The coronal sections of the brains were prepared and stained with 2% TTC, and the infarct volumes were determined. Another 54 male rats were performed as description above except that the brain tissues were made into homogenate at 22 hours of reperfusion, and the contents of lactic acid(LA) and MDA, and the activities of superoxide dismutase(SOD) in the brain tissues were also measured. Results Administration of simvastatin significantly reduced the size of brain infarct, improved neurological deficits, decreased the contents of LA and MDA and increased the activities of SOD, but L-NAME could abrogate these effects. Conclutions L-NAME could abrogate the protection of simvastatin against ischemic/reperfusion injury,which may be by inhibiting the expression and activity of endothelial NO synthase(eNOS) up-regulated by simvastatin.