目的7日龄新生大鼠短暂脑缺血诱导侧脑室室管膜下区(SVZ)神经干细胞增殖,观察胰岛素样生长因子1(IGF-1)对神经干细胞增殖的影响。方法7日龄新生SD大鼠64只,随机分为缺血组(n=24)、假手术组(n=24)、缺血阻断剂组(n=8)和缺血生理盐水组(n=8)。利用免疫组织化学方法观察缺血组和假手术组在缺血后1、4、7dSVZ新生细胞数量和IGF-1表达的变化,并观察缺血阻断剂组和缺血生理盐水组在IGF-1受体阻断剂(JB1)阻断7d后SVZ新生细胞数量和IGF-1表达的变化。结果与同时间点假手术组比较,缺血后1、4、7d的SVZ新生细胞和IGF-1阳性细胞数量均显著增加,差异有统计学意义(P〈0.05);使用JB1后,缺血阻断剂组IGF-1的表达被阻断,IGF-1阳性细胞缺如,而缺血生理盐水组IGF-1表达正常;使用JB1后,缺血阻断剂组SVZ新生细胞数量显著减少,与缺血生理盐水组相比,差异有统计学意义(P〈0.05)。结论新生大鼠缺血再灌注损伤上调了IGF-1的表达,IGF-1表达增加促使SVZ神经干细胞增殖;使用JB1后,IGF-1的表达被阻断,神经干细胞增殖也显著减少,提示IGF-1在脑缺血损伤修复中起关键作用。
Objective To study the impact of insulin-like growth factor 1 (IGF-1) on the neural stem cell proliferation of the subventricular zone (SVZ) induced by transient forebrain ischemia in postnatal day 7 rats. Methods A total of 64 postnatal day 7 Sparuge-Dawley rats were randomly divided into ischemia group ( n = 24) , sham group( n = 24) , ischemia plus antagonist group ( n = 8) and ischemia plus saline group ( n = 8). The cell proliferation and IGF-1 in the SVZ of the ischemia group and the sham group were observed 1, 4 or 7 days after ischemia with immunohistochemical staining. The cell proliferation and IGF-1 in the SVZ of the ischemia plus antagonist group and the ischemia plus saline group were detected after 7 days of continuous treatment with JB1 or without JB1 treatment. Results The number of BrdU + cells and IGF-1 + cells of the ischemia group were significantly increased in the SVZ 1, 4, and 7 days after ischemia compared with that of the sham group (P 〈 0. 05). After the administration of JBI, the IGF-1 expression was blocked. The IGF-1+ cells were absent in ischemia plus antagonist group, while the IGF-1 expressed normally in ischemia plus saline group. The number of BrdU +cells in the ischemia plus antagonist was sharply decreased compared with the ischemia plus saline group ( P 〈 0.05 ) in the SVZ 7 days after ischemia. Conclusion Ischemia/perfusion up-regulates the expression of IGF-1 in neonatal rats, which may promote the proliferation of neural stem cells. Decrease of the neural stem cells proliferation dramatically after the administration of JB1 suggests that IGF-1 may play a key role on recovery of transient forebrain ischemia damage.