小剂量一氧化氮合酶抑制剂对局灶性脑缺血神经细胞损伤的影响

背景:一氧化氮在神经系统中的作用是近10年来的研究热点之一,而其在脑缺血过程中对神经细胞的损伤的何保护性作用?目的:研究一氧化氮在局灶性脑缺血再灌流过程中对病理改变的影响,并探讨其机制。设计:完全随机对照开放实验。地点和对象:实验地点:吉林大学第一医院神经科研究室;研究对象:Wistar大鼠70只,雌雄各半,体质量200～250g,由本校实验动物部提供。干预:利用N-硝基-左旋-精氨酸(N-nitro-L-arginine,NNLA)干预局灶性大鼠脑缺血模型。主要观察指标:通过光、电镜及未端脱氧核糖核酸介导生物素化脱氧尿嘧啶缺口未端标记(terminaldeoxyribonucleotidetransferase-mediateddUTP-biotinnickend-labeling,TUNEL)法观察局灶脑缺血大鼠脑组织的病理学改变。结果:缺血再灌1d时光镜下皮质、海马区均可见神经细胞呈坏死样改变;电镜下半影区神经细胞的改变仅见于核染色质凝集(类似凋亡小体)和小胶质细胞核变形,以细胞凋亡为主;小剂量给予NNLA干预后坏死和凋亡的病理改变均较手术对照组轻(P<0.01)。TUNEL显示与病理改变结果一致(P<0.01)。结论:局灶性脑缺血后,调节一氧化氮生成量在适当范围,可以保护、防止神经细胞进一步损伤。

Impact of small dose of inhibitor of nitric oxide synthase on neuronal damage in focal cerebral ischemic rats

BACKGROUND: The reaction of nitric oxide(NO) in neural system is one of the hot areas in the researches during the recent ten years. However, what kind of protective reaction does NO have against neuronal damage in the process of cerebral ischemia?OBJECTIVE: To study the impact of NOon the pathological changes during the process of focal cerebral ischemia-reperfusion and to discuss its mechanism. DESIGN: A completely randomized controlled open study.SETTINGS and MATERIALS: Settings: Department of Neurology of the First Hospital affiliated to Jilin University. Materials: Seventy Wistar rats of 35 rats in each gender with a body mass from 200 g to 250 g were obtained from the department of experimental animal of our university.INTERVENTION: Focal cerebral ischemia rat model was intervened by N-nitro-L-arginine (NNLA).MAIN OUTCOME MEASURES: Pathological changes in focal is chemic brain tissue in rat were observed by optical and electric microscope as well as terminal deoxyribonucleotide tranferase-mediated dUTP-biotin nick end-labeling (TNUEL) techique.RESULTS: At one day after ischemia-reperfusion, neuronal necrotic changes could be seen in hippocampus under optical microscope; The pathological changes of chromatin condensation(apoptotic body) and deformation of small glial cellular nucleus that mainly were apoptosis were seen in neurons in ischemic penumbra under electric microscope. After the intervention of small dose of NNLA, the pathological changes of necrosis and apoptosis were milder than those of control group( P ＜ 0.01) and the results of TUNEL were in accordance with pathological results( P ＜ 0.01).CONCLUSION: It can protect and prevent further neuronal damages by adjusting the production of NO within a proper range after focal cerebral ischemia-reperfusion.