脉络宁抑制氧化应激保护缺血性脑损伤

目的 探讨脉络宁对氧化应激和缺血性脑损伤的影响.方法 健康雄性昆明小鼠126只,分为假手术组(n=18)、生理盐水对照组(n=54)和脉络宁组(n=54).建立大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)模型,脉络宁组和生理盐水对照组MCAO 2 h后分别经尾静脉给予脉络宁注射液和同体积生理盐水,然后每隔24 h重复1次.在MCAO 12、24和72 h分别进行神经功能评分、脑水含量、梗死体积、膜电位以及蛋白质氧化应激代谢产物3-硝基酪氨酸(3-nitrotyrosine,3-NT)、脂质氧化应激代谢产物4-羟基壬烯醛(4-hydroxy-2-nonenal,HNE)和核酸氧化应激代谢产物8-羟基脱氧鸟苷(8-hydroxy-2'-deoxyguanosine,8-OHdG)检测.结果 在脑缺血后不同时间点,脉络宁注射液均可显著改善脑缺血小鼠的神经功能、减轻脑水肿和缩小梗死体积,其中以72 h最为显著;脉络宁注射液可逆转脑皮质和内囊区的线粒体膜电位降低,显著下调缺血后皮质、内囊和血清3-NT、HEN 和8-OHdG的升高,其中以降低HNE效果最为显著.结论 脉络宁注射液能有效保护小鼠缺血性脑损伤,其机制与抑制氧化应激,尤其是抗脂质氧化有关.

Mailuoning protects against ischemic brain injury by inhibiting oxidative stress

Objective To investigate the effects of Mailuoning on oxidative stress and ischemic brain injury. Methods A total of 126 healthy male Kunming mice were divided into sham operation (n = 18), normal saline control (n = 54) and Mailuoning (n = 54) groups. A middle cerebral artery occlusion (MCAO) model was induced Two hours after MCAO,Mailuoning injection and equivalent saline were injected via the tail vein in the Mailuoning and normal saline control groups, respectively, and then they were injected every other 24 h.Neurological score was performed, and brain water content, infarct volume, membrane potential,as well as protein oxidative stress metabolites such as 3-nitrotyrosine (3-NT), lipid oxidative stress metabolite 4-hydroxy-2-nonenal (HNE) and nucleic acid oxidative stress metabolite 8-hydroxy-2'-deoxyguanosine (8-OHdG) were detected at 12, 24 and 72 h after MCAO. Results Mailuoning injection could significantly improve the neurological function of cerebral ischemia in mice, decrease brain edema, and reduce infarct volume at different time points after cerebral ischemia Of those, it was most significant at 72 h. Mailuoning injection could reverse the decreased mitochondrial membrane potential in cerebral cortex and internal capsule, and significantly downregulate the increased 3-NT, HNE and 8-OHdG in cerebral cortex, internal capsule and serum after ischemia, of those, the effect of reducing HNE was most significant.Conclusions Mailuoning injection may effectively protect against ischemic brain injury in mice,and its mechanism is associated with inhibiting oxidative stress, particularly anti-lipid oxidation.