L-NAME对SIM治疗脑缺血/再灌注损伤保护作用的影响

Pre-ischemic Administeration of L-NAME Abrogates the Protection of Simvastatin Against Ischemic/Reperfusion Injury in Rats

目的 研究一氧化氮合酶 (NOS)抑制剂左旋硝基精氨酸甲酯 (L -NAME)对辛伐他汀 (Simvastatin ,Sim)治疗脑缺血 /再灌注损伤保护作用的影响。方法 ①采用ZeaLonga法制作大鼠大脑中动脉阻塞 (MCAO)模型。② 5 4只雄性大鼠以辛伐他汀或其溶媒灌胃治疗 2w ,于MCAO手术前 45min ,经侧脑室注射L -NAME ,MCAO 2h再灌注 2 2h对大鼠进行神经功能缺陷评分 ,随后大鼠取脑制冠状切片 ,氯化三苯基四氮唑 (TTC)染色后测量脑梗死体积。另取 5 4只雄性大鼠操作同上 ,再灌注 2 2h取脑制成匀浆 ,测量脑组织中乳酸 (LA)、丙二醛 (MDA)含量以及超氧化物歧化酶 (SOD)活性。结果 辛伐他汀治疗可缩小大鼠MCAO后的脑梗死体积 ,改善神经功能 ,减少脑组织内LA和MDA生成 ,升高SOD活性 ,L -NAME可取消辛伐他汀的上述作用。结论 辛伐他汀对大鼠脑缺血 /再灌注损伤有保护作用 ,L -NAME可取消这一作用 ,其机制可能与L -NAME抑制辛伐他汀上调eNOS基因表达和活化作用有关。

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.