caspase-3在海马损伤后齿状回神经发生调控中的作用

目的探讨成年大鼠海马CA1区损毁后,齿状回（DG）细胞先增殖后减少的原因。方法用海人酸（KA）建立单侧海马损毁模型;用5-溴脱氧尿嘧啶核苷（BrdU）标记海马DG区增殖的细胞,用免疫组织化学方法检测标记后不同时间点DG区BrdU阳性细胞,并用无偏差体视学方法定量分析;激光共聚焦显微镜检测BrdU与裂解的caspase-3的共表达。结果实验组动物在损毁海马后各时间点DG区BrdU阳性细胞总数均比对照组明显增多,差异有统计学意义（P〈0.05）;各组动物BrdU阳性细胞总数在标记后第1天最多,随着时间的延长逐渐减少;在颗粒细胞层和门区均有少量BrdU/cleaved caspase-3共表达的阳性细胞。结论损毁成年大鼠海马CA1区后,增殖的细胞总数随着时间的延长逐渐减少,其机制可能与caspase-3相关的细胞死亡及异位迁移有关。

Role of Caspase 3 in the Controls of Neurogenesis in Dentate Gyrus After Hippocampal Lesion

Objective To investigate the cause of the reduction of proliferating cells in the dentate gyrus （DG） after hippocampus CA1 lesion in adult rats. Methods Adult rats were used to establish unilateral hippocampus lesion by intrabippocampal microinjection of kainic acid; 5-bromodeoxyuridine（BrdU） was used to label the proliferating cells. The BrdU-positive cells in DG after hippocampal lesion were identified by immunohistochemistry at various time points and the number of BrdU-positive cells in DG was estimated by stereological method. The co-expression of BrdU and cleaved caspase-3 was observed using the laser confocal fluorescence microscopy. Results Quantitative analysis revealed that comparing with that of controls, in the experimental group there were obvious more BrdU-positive cells in DG at each time point after hippocampal lesion;in the each group there were the most BrdU-positive cells on the first day after administration of BrdU and they gradually reduced with time went by; there were few BrdU/cleaved caspase-3 double-labelled cells both in the granular cell zone and the hilus. Conclusion The total number of the proliferating cells reduce with time after hippocampal lesion in adult rats, its mechanisms may be related to caspase-3-induced cell death and ectopic migration.