大鼠空肠胰岛素样生长因子-1信号转导的增龄性变化

Study of the changes in signal transduction of insulin-like growth factor-1 in jejunum of aging rats

目的探讨空肠胰岛素样生长因子-1(IGF-1)信号转导的增龄性变化。方法雄性SD大鼠104只,按不同发育阶段分组。采用免疫组化染色、Western印迹法测定空肠IGF-1、胰岛素受体底物1(IRS-1)、磷脂酰肌醇3激酶(PI3-K)、蛋白激酶B(Akt)、磷酸化的cAMP反应元件结合蛋白(p-CREB)变化。结果自1月龄开始空肠IGF-1逐渐增加,至6月龄达到高峰,然后逐渐降低,24月龄大鼠空肠IGF-1最低。空肠IRS-1、Akt、p-CREB也出现相同的变化趋势,IRS-1在12、18、24月龄维持于较低的水平,虽然Akt于6月龄表达最强,但仅显著高于24月龄。然而PI3-K则与IGF-1相反,1月龄为最低,其后逐渐升高,至24月龄达高峰。结论随着增龄老年动物空肠IGF-1促细胞生长信号转导显著下调。

Objective To explore the change in signal transduction of insulin-like growth factor-1 （IGF-1） in jejunum with aging. Methods 104 SD male rats were divided into 6 groups according to different growth stages. The changes in IGF-1, insulin receptor substrate 1, phosphoinositide 3-kinase （PI3-K）, protein kinase B （PKB/Akt）, phosphorylation cAMP response element bindin （p-CREB） in jejunum were measured by immunohistochemistry and Western-blotting. Results Jejunal IGF-1 raised gradually from the 1st month, reached the peak in the postnatal 6th month, then decreased gradually. Jejunal IGF-1 of rats at the 24th month reached to the minimum. The changes of Jejunal IRS-1, Akt and p-CREB presented the same trend. IRS-1 maintained lower level at the 12th, 18th and 24th month. The expression of Akt was the maximum at the 6th month, while it was significantly more at the 6th month than that at the 24th month. Nevertheless, the change of PI3-K was opposite to that of IGF-1. Jejunal PI3-K at the 1st month was the minimum, then increased gradually and reached peak at the postnatal 24th month. Conclusions With aging, the cellular growth signal transduction stimulated by IGF-1 could be downregulated dramatically in the aged animals.