CAJ | 학술논문

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。
목적：탐토12／15－LOX억제제거갑이경화유창목산（ nordihydroguaiaretic acid ，NDGA）시부구유대항결혈／재관주손상적뇌보호작용。방법체내실험부분：선전법（ MCAO）제비대서뇌결혈／재관주손상모형，수궤분위NDGA처리조、용제대조조（ DMSO）급가수술조。수선대각조대서진행신경공능평분，병진행조간비교；기차채용TTC법비교각조동물뇌경사체적적차이。체외실험부분：제비대서피층신경원당양박탈（ OGD）세포모형，수궤분위OGD＋NDGA조、OGD＋용제대조조급공백대조조。분별채MTT법화TUNEL 법검측각조신경원적세포활력화조망정황，병진행조간비교。결과체내실험결과현시NDGA처리조여용제대조조상비，신경공능결손현저개선（ P＜0．05），경사체적백분비현저감소（ P＜0．05）。체외실험결과현시NDGA가현저제고OGD재합양후적신경원존활솔（ P＜0．05），동시NDGA처리조TUNEL양성세포비솔역명현강저（ P＜0．05）。결론12／15－LOX억제제NDGA능구개선결혈／재관주손상대서적신경공능결손，감소경사체적，제고결혈／재관주손상후신경원적존활솔，억제신경원세포조망，인차구유대항결혈／재관주손상적뇌보호작용。
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<0.05 ) and in-farct volume ( P <0.05 ) were significantly reduced by pretreatment with NDGA. In vitro, NDGA significantly increased cell viability after OGD in neurons ( P<0.05 ) and the amount of TUNEL positive cells in NDGA treatment group was much lower than that of control group ( P<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.