NDGA对脑缺血/再灌注损伤的脑保护作用  

Protective effects of nordihydroguaiaretic acid on the cerebral ischemia and reperfusion injury

作　　者：朱延梅[1] 陈莉[1] 刘羽[1] 朱雨岚[1] 

机构地区：[1]哈尔滨医科大学附属第二医院神经科,黑龙江哈尔滨150081

出　　处：《哈尔滨医科大学学报》2014年第6期455-459,共5页Journal of Harbin Medical University

基　　金：黑龙江省教育厅科学技术研究项目资助(11551217)

摘　　要：目的探讨12/15-LOX抑制剂去甲二氢化愈创木酸(nordihydroguaiaretic acid,NDGA)是否具有对抗缺血/再灌注损伤的脑保护作用。方法体内实验部分:线栓法(MCAO)制备大鼠脑缺血/再灌注损伤模型,随机分为NDGA处理组、溶剂对照组(DMSO)及假手术组。首先对各组大鼠进行神经功能评分,并进行组间比较;其次采用TTC法比较各组动物脑梗死体积的差异。体外实验部分:制备大鼠皮层神经元糖氧剥夺(OGD)细胞模型,随机分为OGD+NDGA组、OGD+溶剂对照组及空白对照组。分别采MTT法和TUNEL法检测各组神经元的细胞活力和凋亡情况,并进行组间比较。结果体内实验结果显示NDGA处理组与溶剂对照组相比,神经功能缺损显著改善(P<0.05),梗死体积百分比显著减小(P<0.05)。体外实验结果显示NDGA可显著提高OGD再合氧后的神经元存活率(P<0.05),同时NDGA处理组TUNEL阳性细胞比率亦明显降低(P<0.05)。结论 12/15-LOX抑制剂NDGA能够改善缺血/再灌注损伤大鼠的神经功能缺损,减少梗死体积,提高缺血/再灌注损伤后神经元的存活率,抑制神经元细胞凋亡,因此具有对抗缺血/再灌注损伤的脑保护作用。Objective To explore the cerebral protective effect of 12/15-lipoxygenase （12/15-LOX） inhibitor, nordihydroguaiaretic acid （NDGA）.Methods A rat model of transient mid-dle cerebral artery occlusion （ MCAO ） and reperfusion was made for the in vivo experiment. The animals were divided into three groups：NDGA treatment group, solvent （DMSO） control group and sham-operation group. Firstly, the neurological score was assessed and compared a-mong the three groups. Secondly , the infarction volume was measured by 2 ,3 , 5-triphenyltet-razolium chloride （TTC）-staining.Oxygen-glucose deprivation （ OGD） was performed in cul-tured rat cortical neurons for the in vitro experiment. The cells were divided into three groups：OGD＋NDGA treatment group, OGD ＋solvent control group and placebo control group. The cell viability and apoptosis were examined respectively by MTT and TUNEL method. Re sulst In vio , in contrast to the cases treated with solvent , the neurologic deficits （ P＆lt;0.05 ） and in-farct volume （ P ＆lt;0.05 ） were significantly reduced by pretreatment with NDGA. In vitro, NDGA significantly increased cell viability after OGD in neurons （ P＆lt;0.05 ） and the amount of TUNEL positive cells in NDGA treatment group was much lower than that of control group （ P＆lt;0.05 ）. Conclusion NDGA, the inhibitor of12/15-LOX , improves neurological deficits , and reduces infarct volumes after MCAO in rats. It also increases cell viability and inhibits apopto-sis after OGD in neurons. Thus NDGA has a cerebral protective effect against I/R injury.

关 键 词：去甲二氢愈创木酸 12/15脂氧酶 脑保护作用 缺血/再灌注损伤 

分 类 号：R743[医药卫生—神经病学与精神病学]