脑缺血再灌注后脑组织Cyclin D1和CDK4基因的表达及其意义  

EXPRESSION OF GENE Cyclin D1 AND CDK4 IN BRAIN TISSUE AFTER CEREBRAL ISCHEMIA REPERFUSION IN RATS

作　　者：刘宏[1] 郭云良[2] 

机构地区：[1]青岛市精神卫生中心,山东青岛266034 [2]青岛大学医学院脑血管病研究所

出　　处：《齐鲁医学杂志》2005年第3期231-233,共3页Medical Journal of Qilu

基　　金：山东省自然科学基金资助项目(Y2001C04)

摘　　要：①目的研究脑缺血再灌注后细胞周期蛋白D1(CyclinD1)和周期蛋白依赖性蛋白激酶4(CDK4)基因表达及其与神经细胞凋亡的关系。②方法成年健康雌性SD大鼠36只,随机分为假手术组4只和实验组32只,实验组再进一步分为缺血1.5h再灌注2h、6h、12h、1d、2d、3d、7d和14d亚组,每组4只。应用线栓法经左侧颈外颈内动脉插线建立SD大鼠大脑中动脉阻塞(MCAO)再灌注模型,应用原位末端标记(TUNEL)技术检测脑缺血再灌注后神经细胞凋亡的变化,原位杂交技术检测CyclinD1mRNA和CDK4mRNA的表达。③结果脑缺血再灌注2h脑组织即开始出现凋亡神经细胞,并于1d和2d分别在皮质区和纹状体区达高峰。神经细胞CyclinD1mRNA和CDK4mRNA的表达分别于再灌注2h和6h开始逐渐增强,并于12h和1d分别在皮质区和纹状体区达高峰,至再灌注14d降至假手术组水平。④结论脑缺血再灌注后皮质区、纹状体区对缺血更为敏感,CyclinD1mRNA和CDK4mRNA表达可能是诱导细胞凋亡的重要因素之一。Objective To investigate the relationship between the expressions of Cyclin D1 and cyclin-dependent kinase 4（CDK4） and neuronal apoptosis after focal cerebral ischernia reperfusion in rats. Methods Thirty-six adult healthy fernale SD rats were randornly divided into sham-operated group （n=4） and experirnental group （n=32）, the latter was further divided into 2-,6- ,and 12-hour, and 1-, 2 , 3-, 7- and 14 day reperfusion subgroups after ischemia for 1.5 .hours. The model of focal ischernia reperfusion was established by intraluminal middle cerebral artery occlusion （MCAO） with a nylon monofilament suture through left external-internal carotid artery. The neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated 5＇dUTP nick end-labeling （TUNEL） staining. In situ hybridization was performed to examine the expressions of Cyclin D1 mRNA and CDK4 mRNA. Results TUNEL-positive neurons appeared at two hours of reperfusion and peaked at one and two days in the cortex and striatum, respectively. Cyclin D1 mRNA expression was detected in the cortex and striaturn of ischernic hemisphere as early as two hours after reperfusion, while CDK4 mRNA was detected at six hours, and reached the highest levels at 12 hours and one day in the cortex and striatum, respectively, and then decreased to sham operated level at 14 days of reperfusion. Conclusion The cortex is more sensitive to ischemia than the striatum. The expressions of Cyclin D1 and CDK4 rnRNA might be one of important factors inducing apoptosis in cerebral ischernia reperfusion.

关 键 词：脑缺血 细胞凋亡 基因表达 细胞周期蛋白D1 细胞周期蛋白质依赖激酶类 

分 类 号：R361.2[医药卫生—病理学]