摘要目的 观察缺氧缺血(HI)对3日龄大鼠脑细胞凋亡及成年后头部MRI影像和学习记忆能力的影响.方法 应用凋亡基因芯片研究3日龄大鼠缺氧缺血性脑损伤后12 h与损伤7 d凋亡基因表达的差异.42日龄时进行大脑MRI检查,并在44日龄时采用水迷宫测试其学习和记忆能力.组间比较采用t检验和秩和检验.结果 与HI脑损伤后12 h相比,损伤后7 d表达上调的基因包括TNF及其受体家族中的Tnfsf10(TRAIL)、Tnfsf13(CD30)、Tnfrsf21、Tnfrsf11b;Caspase家族中的Caspase1、2、3和6;Bcl2家族中的促凋亡基因Bak1、Becn1、Bcl10和Bid3;死亡域TRADD和Myd88.而Caspase 8和抗凋亡基因Mapk8ip表达下调.42日龄时头部MRI检查显示HI组右侧大脑皮质面积较左侧和假手术组显著减小[侧脑室层(23.5±3.6)mm2、(33.0±4.3)mm2和(34.5±3.9)mm2(F=17.09,P<0.01);海马层(18.9±4.4)mm2、(29.1±5.0)mm2和(30.8±4.5)mm2(F=14.44,P<0.01)].HI组水迷宫试验上台时间在第4天为(52.7±35.9)s,明显长于假手术组的(17.8±8.9)s(P<0.01).记忆测试中,HI组大鼠经过站台的次数显著少于假手术组(T=292.5,P<0.05).结论 3日龄SD大鼠HI脑损伤后,神经细胞凋亡基因激活持续到损伤后7 d,涉及凋亡的外源性和内源性通路.神经细胞的凋亡会导致大脑皮层萎缩,可能影响动物成年后的空间学习和记忆能力.

abstractsObjective To investigate the activation of apoptotic genes of the brain with hypoxia- ischemia (HI) in newborn SD rats, and MRI changes and memory and learning ability in adulthood. Methods HI was induced by right carotid artery ligation followed by 2.5 h of hypoxia (6% O2) on 3-day-old SD rats (n=36). Control pups were sham-operated (n = 27). Right brain hemisphere was collected at 12 h and 7 d after HI and subjected to an apoptosis Oligo GEArrayR. MRI and Morris water maze test were performed on both groups at 42 and 44 days old, respectively. Results Comparing to 12 h after HI, up-regulated apoptotic genes included TNF, Caspase and pro-apoptotit genes of Bcl2 families, whereas the anti-apoptotic genes of Bcl2 family were down-regulated at 7 d after HI. The MRI assessment of the rats in HI group demonstrated that the area of the right cerebra l cortex was significantly smaller than the left side and control [periventricular layer: (23.5±3.6) mm2 vs (33.0±4.3) mm2, (34.5±3.9) mm2; hippocampus layer: (18.9±4.4) mm2 vs (29.1±5.0) mm2,(30.8±4.5) mm2, both P<0.01]. During the navigation trial, the HI rats demonstrated longer escape latency (4th day: (52.7±35.9) vs (17.8±8. 9) s, P<0.01). HI rats passed the platform less times than the control ones (T= 292.5, P<0.05) in space probe trial. Conclusions The activation of apoptotic genes induced by HI brain injury remains until 7 days later, involving intrinsic and extrinsic apoptotic pathway. The apoptosis of neural cells may lead to poor development of the cortex and impair the memory and learning ability in the adult rats after neonatal hypoxia- ischemia injury.