慢性脑缺血致认知功能障碍大鼠神经细胞Caspase-3表达及GDNF给药的影响

目的观察慢性脑缺血后致认知功能障碍大鼠神经细胞半胱氨酸蛋白酶(Caspase-3)表达,并探讨胶质细胞源性神经营养因子(GDNF)对大鼠认知功能障碍和Caspase-3表达的影响。方法采用双侧颈总动脉永久结扎方法制备慢性前脑缺血大鼠模型,随机分为对照组、GDNF组和生理盐水组,分别在术后1月、2月,根据逃避潜伏期对各组大鼠进行记忆功能测定,应用免疫组织化学方法检测Caspase-3表达。结果双侧颈总动脉结扎1、2月组与对照组相比,逃避潜伏期明显延长;GDNF组与生理盐水组比较,逃避潜伏期明显缩短;与对照组相比,缺血组大鼠额叶皮层、海马的Caspase-3阳性细胞数明显增多,与生理盐水组比较,1、2月GDNF组大鼠额叶皮层、海马的Caspase-3阳性细胞数明显减少。结论GDNF可改善认知功能,其机制可能是通过影响Caspase-3凋亡关键蛋白酶表达,抑制神经细胞凋亡。

Expression of Caspase-3 in Brain of Rat with Cognition Dysfunction Caused by Chronic Cerebral Ischemia and Effect of Glial Cell Line-derived Neurotrophic Factor

Objective To observe the expression of cysteinyl aspartate specific protease-3(Caspase-3) in brain of rat with cognition dysfunction cause by chronic cerebral ischemia and explore the effect of glial cell line-derived neurotrophic factor(GDNF) on cognition clysfunction and the expression of Caspase-3.Methods Establish rat model of chronic cerebral ischemia by permanent deligation of bilateral common carotid artery.Divide model rats into GDNF and physiological saline groups and treat with GDNF and physiological saline for 7 d respectively,using the rats without deligation of common carotid artery as control.Determine the cognition function of rats 1 and 2 months after deligation respectively with escape latent period,and the expression of Caspase-3 by immunohistocheical method.Results The escape latent periods of rats 1 and 2 months after deligation of common carotid artery were longer than that of control.Compared with that treated with physiological saline,the escape latent period of model rats treated with GDNF was shortened significantly.The numbers of Caspase-3 positive cells in frontal lobe cortical layer and hippocamp of model rats were significantly higher than that in control.However,the number in model rats treated with GDNF decreased significantly 1 and 2 months after deligation of common carotid artery as compared with that treated with physiological saline.Conclusion GDNF might improve the cognition function of rats by influencing the expression of Caspase-3 and inhibiting the apoptosis of nerve cells.