Protective Effect Of IGF-1 On Learning And Memory Of OSAS Rats And Its Mechanism

Objective: The aim of this work is to observe the effect of IGF-1 on learning and memory and the expression of IGF-1,p-IGF-1R and SYP protein in hippocampus of OSAS rats and to explore its primary mechanism.Methods: Forty adult male Sprague-Dawley rats were randomly divided into blank control group,OSAS model group,treatment control group and IGF-1 treatment group.The chronic intermittent hypoxia was used to simulate the OSAS rat model.The rats in IGF-1treatment group were injected with IGF-1(50?g/kg)into the abdomen subcutaneously every day before the model and treatment control group received 0.9% normal saline(1ml/kg)at the same time,while the blank control group without any treatment.The model was finished four weeks later.The Morris water maze was used to compare the spatial learning and memory abilities of rats in each group.The pathological changes of hippocampal neurons in each group were observed by HE staining.The levels of IGF-1protein in the hippocampus were determined by ELISA.IHC detection of p-IGF-1R and SYP protein localization and expression in hippocampus.Finally,Western blot was used to detect the expression of p-IGF-1R and SYP protein in hippocampus of rats in each group.Results: Compared with reoxygenation intervels,the Sp O2 of caudal artery in hypoxia rats decreased significantly and the overall range of Sp O2 decreased by more than 4%(P<0.05).During the modeling period,the rats showed head-up respiration,accelerated abdominal respiration,and accelerated daytime,which accords with the standard of OSAS model.In Morris water maze test,compared with the blank control group,the escape latency of the OSAS model group was significantly prolonged(P<0.05),and the number of crossing the original platform significantly increased(P<0.05);compared with the OSAS model group,the escape latency of the IGF-1 treatment group was significantly shorter(P<0.05),and the number of crossing the original platform significantly increased(P<0.05).In the enzyme-linked immunosorbent assay,the level of IGF-1 protein in the hippocampus of the blank control group and the IGF-1 treatment group was significantly higher than that of the OSAS model group(P<0.05).The results of HE staining showed that hippocampal neurons in blank control group were arranged neatly and tightly,with regular cell morphology,clear structure,light cytoplasm,central nucleus and obvious nucleoli;In OSAS model group,hippocampal neurons in rats were arranged in disorder and sparse and cell size and morphology were irregular;the cell body is swollen and deformed,the cell membrane is crinkled,the cytoplasm is deeply dyed,and the nucleus can be found to shrink and cleavage;In IGF-1 treatment group,the neurons in the hippocampus of rats were also arranged in a few disorder and cytoplasmic deep staining,but the degree was lower than that in OSAS group.In immunohistochemical staining,p-IGF-1R protein showed brown-yellow heterochromatic particles in rat hippocampus,mainly in the CA3 region of the neuronal cell envelope and a small amount of expression in the CA1 region;The level of p-IGF-1R protein in hippocampus of OSAS model group was significantly lower than that of blank control group(P<0.05)and the level of p-IGF-1R protein in hippocampus of IGF-1 treated group was significantly higher than that of OSAS group(P<0.05).SYP protein also showed brownish-yellow-colored particles in rat hippocampus,which was mainly expressed in neurites of CA1 and CA3 regions.The expression of SYP protein in hippocampus of OSAS model group was significantly lower than that of blank control group(P<0.05).The expression of SYP protein in hippocampus of IGF-1 treatment group was significantly higher than that of OSAS model group(P<0.05).In Western blotting experiments,the expression levels of p-IGF-1R and SYP protein in the hippocampus of OSAS rats were significantly lower than those in the blank control group(P<0.05);the hippocampus p-IGF-1R and SYP in the IGF-1 treatment group.Protein expression levels were significantly higher than those in the OSAS model group(P<0.05)Conclusion: IGF-1 can improve the learning and memory ability of OSAS rats,which may be related to the increased expression of p-IGF-1R and SYP proteins in hippocampus.