自噬在海马损伤后齿状回神经发生调控中的作用

目的探讨成年大鼠单侧海马CA1区毁损后,海马齿状回（DG）神经发生新生细胞存活与自噬的关系。方法建立海人酸（KA）损毁单侧海马的模型,用5-溴脱氧尿嘧啶核苷（BrdU）于毁损后3d标记增殖的细胞,免疫组织化学检测BrdU阳性细胞,采用体视学的计数方法计算DG的BrdU阳性细胞总数。用自噬特异性抗原微管相关蛋白轻链3（LC-3）与BrdU双标的方法检测这些新生细胞的减少是否有自噬的参与。结果假毁损组DG区可见少量的BrdU阳性细胞;与假毁损组比较,实验组在海马毁损后DG区BrdU阳性细胞明显增加,差异有统计学意义（P〈0.05）,在BrdU给药后第1天最多,随着时间的推移逐渐减少,各组之间差异有统计学意义（P〈0.05）;各时间点均未见BrdU和LC-3双标细胞。结论成年大鼠海马毁损可增强DG的神经发生,新生细胞随着时间的推移逐渐减少,而自噬性程序性细胞死亡在新生细胞减少的调控中可能不占主导作用。

Role of Autophagy in the Control of Neurogenesis in the Dentate Gyrus After Hippocampal Damage

Objective To investigate the relationship between the survival of the newborn cells in the dentate gyrus after unilateral hippocampal lesion and the activation of autophagy in adult rats. Methods Unilateral hippocampal lesion was established by intrahippocampal microinjection of kainic acid. 5-Bromodeoxyuridine（BrdU） was used to mark the proliferating cells, the BrdU-positive cells in the dentate gyrus at different time points were identified by immunohistochemistry and the number of BrdU-positive cells was estimated by stereological method. Doublestaining of autophagy spicifie marker LC-3 and BrdU was used to observe whether the autophagy induces the reduction of newbem cells. Results Quantitative analysis of BrdU-labeling reveals that as compared with the control group, the experimental group＇had the most positive cells in DG on the first day after three-day administration of BrdU. The number of BrdU-positive cells in experi： mental group gradually reduced. BrdU/LC-3 double-labeled cells were not found on each time point after hippocampal damage. Conclusion Hippocampal damage in adult rats can enhance the neuro- gensis in DG, which reduced progressively with time,but the autophagic cell death may not play a major role in the reduction of newbem cells.