L-NAME和格列苯脲对辛伐他汀脑缺血再灌注损伤保护作用的影响  

The ischemic stroke protection of simvastatin be blocked by Pre-ischemic administeration of glibenclamide or L-NAME

作　　者：刘勇[1] 谢立新[2] 宋涛[1] 方芳[2] 董敏[1] 方云祥[2] 杨栋梁[2] 

机构地区：[1]中南大学湘雅二医院精神卫生研究所,湖南长沙410011 [2]中南大学药学院药理学教研室,湖南长沙410078

出　　处：《中国药理学通报》2004年第9期1007-1011,共5页Chinese Pharmacological Bulletin

基　　金：国家"8 63"计划九五课题资助项目;No 10 3 13 0 1 0

摘　　要：目的　研究侧脑室注射左旋硝基精氨酸甲酯 (L NAME)和格列苯脲 (glibenclamide ,Gly)对辛伐他汀 (simvas tatin ,Sim)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。②6 3只♂SD大鼠以 2 0mg·kg-1辛伐他汀或其溶媒灌胃治疗2wk后 ,于MCAO手术前 4 5min ,经侧脑室注射L NAME(10mg·kg-1)或Gly(3mg·kg-1)以及相应溶媒 ,再灌注 4h和 2 2h进行神经功能缺陷评分 ,评分完成立即取脑制成冠状切片 ,TTC染色后测量脑梗死体积。另取 6 3只SD大鼠操作同上 ,再灌注 2 2h取脑制成匀浆 ,测量乳酸 (LA)、丙二醛 (MDA)含量和超氧化物歧化酶 (SOD)活性。结果　辛伐他汀明显缩小大鼠MCAO后的脑梗死体积 ,改善神经功能 ,降低脑组织内LA和MDA含量 ,升高SOD活性 ,L NAME和Gly阻断了辛伐他汀的上述效应。 结论　侧脑室注射L NAME和格列苯脲可阻断辛伐他汀对脑缺血 /再灌注损伤的保护作用 ,辛伐他汀可能通过eNOSAim To investigate the effects of pre-ischemic administration of L-NAME or glibenclamide by lateral ventricle injection 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)63 male rats were treated with simvastatin(20 mg·kg -1) or vehicle by gavage two weeks before MCAO, either L-NAME(10 mg·kg -1)or glibenclamide(3 mg·kg -1) was injected into lateral ventricle of rats 45 minutes before MCAO. Neurological deficits was assesed at 4 and 22 hours of reperfusion, and rats' brain were removed after the last assessment. The coronal section of brain were stained with 2% TTC, and the infarct volumes were determined. Another 63 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), maleic dialdhyde(MDA) and the activities of superoxide dismutase(SOD) in the brain tissues were also measured. Results 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 both L-NAME and glibenclamide could blocked these effects. Conclutions The ischemic stroke protection of high dose of simvastatin could be blocked by glibenclamide, which suggest simvastatin could activate K ATP channels and then achieve the protective effects through the endothelial NO pathway.

关 键 词：辛伐他汀 格列苯脲 L-NAME KATP通道 脑缺血/再灌注损伤 

分 类 号：R-332[医药卫生] R322.81