早期干预对宫内感染致脑损伤仔鼠神经干细胞增殖能力的影响

目的研究早期干预对宫内感染致脑损伤新生大鼠内源性神经干细胞原位增殖能力的影响。方法30只孕17d大鼠连续2d腹腔注射脂多糖(450μg/kg),设为脂多糖组,制备宫内感染脑损伤动物模型,生理盐水组6只注射等量生理盐水。将脂多糖组所产足月新生仔鼠用随机数字表法分为损伤组和训练组,生理盐水组所产仔鼠为对照组,每组各30只。对训练组进行早期干预至日龄28d,对照组、损伤组常规饲养;选取1,3,7,14,28d各组仔鼠用免疫组织化学方法动态检测海马齿状回颗粒层,BrdU阳性细胞的表达。结果(1)出生后1d对照组、训练组、损伤组新生大鼠海马齿状回颗粒层均存在BrdU,对照组显著高于训练组、损伤组(P0.01)。(2)对照组BrdU阳性细胞数3d开始增加,7d达到高峰,14d后下降,28d接近正常成年大鼠水平。(3)早期丰富环境刺激后,训练组大鼠海马齿状回颗粒层BrdU阳性细胞数在3d开始增加,14d达高峰,峰值显著高于对照组水平(P0.01),28d后下降,但仍高于对照组,BrdU阳性细胞数在时间上均呈一过性增高表达。结论宫内感染致大鼠脑损伤可导致内源性神经干细胞增殖能力降低,并较长时间内难以自然恢复;早期干预可激活脑损伤鼠内源性神经干细胞原位增殖能力,推迟高峰出现,延长作用"时间窗"。

The effect of early intervention on NSCs proliferation in brain damage rats after intrauterine infection

Objective To study the impact of early intervention on proliferation of neural stem cells in brain damage rats after intrauterine infection. Methods Totally 36 Wistar pregnant rats were randomly divided into two groups .. LPS（n= 30） and saline（n= 6）. Pregnant rats were consecutively injected with LPS （450μg/kg） or saline on gestation 17 d. Saline neonatal rats were randomly selected as saline group N（n= 30） ,LPS neonatal rat as training group T（n=30） and injury group I（n=30）. The 1 d T group rats were in- terfered by early interventiont. At the same time, the N, I group rats were fed in the routine way. The expression of bromodeoxyuridind（BrdU） were determined by immunohistochemistry at 1,7,14,28 d of all groups. BrdU was used to mark dividing neural stem cells（NSCs） in hippocamp dentate gyrus subgranular zone （SGZ）. Results （1）BrdU-labeled cells could be observed in all groups;I groups and T groups were markedly less than N group（P〈0.01）. （2）The number of positive cells of N group increased at 3 day（P〈0.05） ,approximately six fold with a peak at 7 day,markedly decreased at 28 clay and approched normal level of mature rats. （3）Compared with the N group,the number of positive cells of T group increased strikingly at 3 day（P〈0. 01）,exceeding N group and approximately six fold with a peak at 14 day, then gradually decreased, but still higher than N group at 28 day. The appearance of increasing peak in T group was lengthened,value ascended. Conclusions Our results indicate that the brain damage caused by intrauterine infection can lead to the decrease of proliferation of inherent NSCs. The damage will not recover itself. Early intervention can stimulate the proliferation of inherent NSCs. Early period enriched environment can prolong the development window phase of inherent NSCs.