胰岛素样生长因子-1(IGF-1)对缺氧缺血脑损伤新生鼠内源性IGF-1和IGF-1受体基因表达的影响

目的　胰岛素样生长因子 1(IGF 1)对损伤的神经组织有修复作用 ,但外源性IGF 1是否会抑制内源性IGF 1、IGF 1受体的生成 ,从而减弱IGF 1的神经保护作用尚不明确。本文通过观察IGF 1治疗新生大鼠缺血缺氧脑损伤 (HIBD)后脑IGF 1和IGF 1受体mRNA水平的变化 ,研究IGF 1对HIBD新生大鼠内源性IGF 1、IGF 1受体的影响。方法　制作新生大鼠HIBD模型 ,用原位杂交方法观察HIBD后各时间点海马和大脑皮层IGF 1和IGF 1受体基因表达的动态变化 ,并比较IGF 1治疗组与未治疗组HIBD后 12h、72hIGF 1、IGF 1受体mRNA的表达水平。结果　HIBD后 4 8h海马IGF 1和IGF 1受体mRNA开始升高 ,72h达高峰。损伤后 12 0h ,IGF 1mRNA降至正常水平 ,而IGF 1受体mRNA仍处于较高水平。在皮层 ,IGF 1和IGF 1受体mRNA开始升高时间稍早于海马 ,2 4h上升 ,96h降至正常 ,但是上升幅度相对较小。与未治疗组比较 ,IGF 1治疗后内源性IGF 1表达无明显变化。IGF 1受体的表达在治疗后 12h无明显差别 ,但在 72h时显著增加。结论　HIBD后皮层、海马等脑损伤区的IGF 1和IGF 1受体表达均升高。给予外源性IGF 1后并不降低内源性IGF 1的表达 ,还能刺激IGF 1受体表达增加。

Effects of insulin- like growth factor-1 (IGF-1) on the expressions of IGF-1 and IGF-1 receptor in neonatal rats with hypoxic-ischemic brain damage

Objective The insulin-like growth factor-1 (IGF-1) can protect damaged neurological system, but it is unknown whether exogenous IGF-1 can inhibit the productions of endogenous IGF-1 and IGF-1 receptor. This study aims to observe the changes of the expressions of IGF-1 and IGF-1 receptor mRNA in neonatal rats with hypoxic-ischemic brain damage (HIBD) and to explore the effects of IGF-1 treatment on endogenous IGF-1 and IGF-1 receptor. Methods Seven-day-old rats were subjected to unilateral carotid artery ligation and hypoxia exposure to establish a HIBD model. In situ hybridization was used to observe the changes of the expressions of IGF-1 and IGF-1 receptor mRNA in the injured regions of neonatal rats at differenft time points following HIBD. The expressions of endogenous IGF-1 and IGF-1 receptor mRNA between the HIBD group and the IGF-1-treated group at 12 hrs and 72 hrs following HIBD were compared by semi-quantitative analysis. Results The expressions of IGF-1 and IGF-1 receptor mRNA in the hippocampus began increasing at 48 hrs following HIBD, and reached a peak at 72 hrs. At 120 hrs post-damage, the expression of IGF-1 mRNA decreased to normal, while the expression of IGF-1 receptor mRNA maintained at a high level. In the cortex, the expressions of IGF-1 and IGF-1 receptor mRNA began increasing at 24 hrs post-damage, and decreased to normal at 96 hrs but their increased extent was less than that in the hippocampus. The expression of endogenous IGF-1 mRNA was not changed after IGF-1 treatment compared with the un-treated HIBD group. The expression of endogenous IGF-1 receptor mRNA remained unchanged 12 hrs after IGF-1 treatment, but significantly increased at 72 hrs. Conclusions IGF-1 and IGF-1 receptor mRNA in the cortex and the hippocampus increase after HIBD. Exogenous IGF-1 has no effect on the expression of endogenous IGF-1, but can up-regulate the expression of IGF-1 receptor.