核转录因子-κB在局部脑缺血及再灌注损伤后大鼠脑细胞中的表达及N-乙酰半胱氨酸的干预作用  

Expression of nuclear factor kappa B in rats’cerebral cells after focal cerebral ischemia and reperfusion and the effects of N-acetylcysteine treatment

作　　者：陈立杰[1] 梁松岚[1] 梁庆成[1] 

机构地区：[1]哈尔滨医科大学附属第二医院神经内科,150086

出　　处：《中华神经科杂志》2005年第3期179-182,共4页Chinese Journal of Neurology

基　　金：黑龙江省自然科学基金资助项目(D01 38)

摘　　要：目的　研究核转录因子- κB(nuclearfactorkappaB, NF -κB)在局部脑缺血及再灌注中的作用及N -乙酰半胱氨酸(NAC)预处理的影响。方法　采用大鼠大脑中动脉线栓模型,分为假手术组、6h及24h缺血再灌注组、相应NAC干预组。应用免疫组化法观测NF -κB的表达情况,红四氯氮唑染色测定各组脑梗死体积,脱氧核糖核苷酸末端转移酶介导的缺口末端标记法(TUNEL)检测细胞凋亡。结果　(1)缺血及再灌注后NF- κBp65明显从胞质转移到胞核。NAC干预组[缺血6h及24h再灌注组p65阳性细胞率分别为( 0 .462% ±0 .022% )和( 0 .452% ±0 .015% ) ]较相应生理盐水组[ (0. 563%±0 .028% )和(0 .554%±0 .013% ) ]p65核表达减少(P<0 .01)。(2)缺血6h及24h再灌注NAC干预组梗死体积百分比分别为(8 .39%±2 .54% )和(24. 54%±6 .02% )。相应生理盐水组为(15 .50%±4 .18% )和(32. 22%±3 .99% )。缺血24h组较缺血6h组梗死灶增大,使用NAC各组较注射生理盐水组梗死体积明显缩小(P<0. 01)。(3)NAC预处理组较生理盐水组凋亡细胞减少(P<0 .01)。结论　局灶脑缺血及再灌注能使NF- κBp65活化,参与脑缺血及再灌注损伤。NAC可抑制p65表达,减轻神经损伤,具有脑保护作用。Objective To investigate the expression of nuclear factor kappa B (NF-κB ) in focal cerebral ischemia and reperfusion and effects of N-acetylcysteine (NAC) pretreatment.Methods The focal cerebral ischemia and reperfusion model was made by suture occlusion of right middle cerebral artery. The rats were randomly assigned to nine groups: sham operated group, 6 hours and 24 hours ischemia groups, 6 hours and 24 hours reperfusion groups, corresponding NAC treatment groups. NAC groups’ rats were treated with NAC (150 mg/kg) prior to occlusion. NF-κB p65 were detected by immunohistochemistry. Brain was stained with 1% triphenyltetrazolium chloride for assessment of the volume of infarction. Apoptosis was detected by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL).Results The translocation of NF-κB from cytoplasm to nucleus increased significantly after ischemia and reperfusion. The expression of NF-κB p65 decreased in NAC pretreatment groups, which were respectively (0.462% ± 0.022%) in 6 hours ischemia-reperfusion groups, (0.452% ± 0.015%) in 24 hours ischemia-reperfusion groups, as compared with saline control groups which were (0.563% ± 0.028%) and (0.554% ± 0.013%) (P<0.01). The percentages of cerebral infarct volume of 6 hours, 24 hours ischemia-reperfusion NAC pretreatment groups were (8.39% ± 2.54%) and (24.54% ± 6.02%). The percentages of corresponding saline control groups were (15.50% ± 4.18%) and (32.22% ± 3.99%). The infarct volume of 24 hours groups was bigger than the volume of 6 hours groups. Treatment with NAC led to a significant reduction in infarct size (P<0.01). The apoptotic cells in the NAC groups were reduced as compared with saline control groups.Conclusion NF-κB p65 should be activated and translocated to the nucleus in focal cerebral ischemia and reperfusion. It might play an important role in the ischemia-reperfusion injury. NAC could reduce cerebral tissue damage with inhibiting the expression of NF-κB p65.

关 键 词：再灌注 缺血 生理盐水 NAC NF-κB 表达 N-乙酰半胱氨酸 核转录因子-ΚB 凋亡细胞 核苷酸 

分 类 号：R743.3[医药卫生—神经病学与精神病学]