内源性IGF-1有利于短暂脑缺血损伤新生大鼠海马神经发生

Endogenous insulin growth factor-1 contributes to hippocampal neurogenesis in neonatal rats with transient forebrain ischemia

目的:7日龄新生大鼠短暂脑缺血诱导海马齿状回(dentate gyrus,DG)新生细胞增殖,观察内源性IGF-1对新生细胞增殖的影响。方法:7日龄新生大鼠64只随机分为缺血(BCCA0)组(n=24)、假手术(SS)组(n=24)、缺血阻断剂(BCCAO+JB1)组(n=8)和缺血生理盐水(BCCA0+SS)组(n=8)。用免疫组织化学方法观察BCCAO组和SS组在缺血再灌注后1、4、7 d DG区新生细胞和IGF-1的增殖变化;观察BCCA0+SS组和BCCAO+JB1组在IGF-1受体阻断剂(JB1)阻断7 d后DG区新生细胞和IGF-1的增殖变化。结果:与同时间点SS组比较,缺血再灌注后1、4、7 d的DG区新生细胞和IGF-1阳性细胞数目均显著增加,差异有统计学意义(P<0.05);BCCA0+JB1组IGF-1的表达被阻断,IGF-1阳性细胞数目缺如,而BCCA0+SS组IGF-1表达如常;BCCAO+JB1组DG区新生细胞数目显著减少,与BCCA0+SS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内源性IGF-1的表达,从而促使DG区新生细胞增殖;使用JB1后,IGF-1的表达被阻断,DG区新生细胞增殖也显著减少,提示内源性IGF-1有利于短暂脑缺血损伤新生大鼠海马区域的神经发生。

Objective:To study the impacts of endogenous insulin-like growth factor-1(IGF-1) on hippocampus dentate gyrus(DG) cell proliferation,induced by transient forebrain ischemia,at postnatal day 7in neonatal rats.Methods:Sixty-four neonatal rats at postnatal day 7 were randomly assigned to ischemia group(BCCAO,n = 24),sham group(SS,n = 24),ischemia antagonist treatment group(BCCAO+JB1,n = 8) and ischemia plus saline injection group(BCCAO+SS,n=8),respectively.The cell proliferation and IGF-1 in the DG of groups BCCAO and SS were observed on days 1,4 and 7 after ischemia by using immunohistochemical staining.The cell proliferation and IGF-1 in the DG of groups BCCAO+JB1 and BCCAO+SS were detected at day7.Results:Compared with group SS,reperfusion following ischemia resulted in significantly increased number of BrdU+ cells and IGF-l+cells in the DG of BCCAO group at days 1,4 and 7(all P<0.05).The administration of JB1 led to blockade of IGF-1 expression and lack of IGF-l+cells in group BCCA0+JB1,but not group BCCAO+SS.The number of BrdU+ cells in the DG of BCCAO+JB1 group was markedly decreased compared with group BCCAO+SS(P<0.05).Conclusion:Ischemia/reperfusion injury up-regulates the expression of IGF-1 in neonatal rats leading to cell proliferation.The blockade of IGF-1 and diminished cell proliferation in the DG following the administration of JB1 suggest that endogenous IGF-1 contributes to hippocampal neurogenesis in neonatal rats with transient forebrain ischemia.