摘要
目的观察胶质细胞源性神经营养因子(glial cell line-derived neuro-trophic factor,GDNF)、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)在大鼠脑缺血再灌注时的表达特点,研究二者在脑缺血再灌注中的作用和相关性。方法阻断大鼠大脑中动脉(middle cerebral artery,MCA)血流2小时,再灌注3小时～120小时制成脑缺血再灌注模型。HE染色评价缺血性脑损伤的组织学特点,免疫组织化学(immunohisto-chemistry,IHC)染色观察GDNF、iNOS表达特点。结果再灌注12小时组开始出现神经元不可逆变性,24小时梗死形成。正常组和假手术组未检测到GDNF的表达。再灌注3小时～120小时,在整个再灌注过程中GDNF阳性的细胞数在3小时达到高峰,后逐渐下降,各组与再灌注3小时组比较P<0.01。正常组和假手术组、再灌注3小时组无iNOS阳性的细胞。再灌注12小时～120小时,在整个再灌注过程中,脑组织iNOS阳性细胞在再灌注12小时开始表达,再灌注24小时达到高峰,后逐渐下降。再灌注12小时～120小时各组与正常组、假手术组、3小时组比较P<0.01。再灌注各组与24小时组比较P<0.01。GDNF与iNOS相关性分析采用Spearman秩相关法rs=--0.200,P=0.704提示GDNF、iNOS二者之间无相关性。结论脑缺血后再灌注,变性的神经元不表达GDNF,缺血周边区和非缺血区神经元GDNF表达明显增强,提示GDNF有促进神经元存活作用。缺血再灌注时SGZ区的细胞表达GDNF,活化的小胶质细胞或巨噬细胞可能表达GDNF。iNOS在脑缺血再灌注后12小时开始表达,24小时达高峰,后逐渐下降,其细胞定位以小胶质细胞为主。iNOS与脑缺血再灌注后期神经元损伤有明显关联。GDNF的神经保护作用与抑制iNOS的表达无关,可能与抑制nNOS的活性有关。为临床早期使用GDNF和iNOS抑制剂减少脑损害,提供了一定的参考价值。
Objective To observe the expression and correlation of glial cell line-derlved neurotrophic factor（GDNFO and inducible nitric oxide synthase（iNOS） in cerebral ischemia tissue of rats after reperfusion. Methods The model of focal cerebral ischemia was made by occluding middle cerebral artery（MCAO for 2h and reperfusion for 3-120h, HE staining was used to investigate the histological features of ischemic cerebral damage, and the immunohistochemical method to observe the expression of GDNF and iNOS in brain tissue of rats. Results The neurons presented irreversible degeneration at 12h of reperfusion. At 24h, the ischemic area in the preoptic area, striatum and cortex developed into infarct form. GDNF positive cells were not detected in normal and sham-operated rats. During the course of reperfusion , the number of GDNF positive cells peaked at 3h of reperfusion, then gradually decreased. Quantitative analysis revealed that the number of GDNF immunoreactive cells in the ipsilateral-ischemic area significantly（P〈0.01） decreased at 12h, 24h, 48h, 72h and 120h afterMCA occlusion compared with that at 3h. The iNOS positive cells were not detected in nomal and sham-operated and 3h of reperfusionrats, they appeared at 12h of reperfusion, peaked at 24h of reperfusion, and then gradually decreased the number of iNOS immunoreactive cells in theipsilateral-ischemic area revealed significantly （P〈0.01） decreased at 48h, 7211, and 120h afterMCA, occlusion reperfusion compared with that at 24h quantitative analysis. Moreover,the number of iNOS immunostaining cell in ischemic area significantly （P,0.01） increased at 24h after MCA occlusion compared with the control groulb,there was no correlation beteew GDNF and iNOS （rs=-0.200 P=0.704）. Conclusion During cerebral ischemia-reperfusion, the degenerative and died neurons did not express GDNF＇ but the neurons in peri-ischemic area and no-ischemic area showed GDNF immunoreactivity. These results suggest that GDNF may have a potential to predispose to reco
出处
《实用心脑肺血管病杂志》
2007年第10期733-737,共5页
Practical Journal of Cardiac Cerebral Pneumal and Vascular Disease
关键词
脑缺血
再灌注
神经营养因子
Cerebral ischemia Reperfusion Neurotrophic factor
