Expression And Mechanism Of GFAP In Hippocampus Of OSAS Rats

Objective:To explore the intrinsic relationship between P-STAT3(S727),GFAP and astrocytes and their role in the development of cognitive impairment in OSAS rats.Methods: Forty-eight male adult Sprague-Dawley rats were randomly divided into four groups: normal control group,OSAS model group,AG490(JAK2/STAT3 signaling pathway inhibitor)intervention group,and DMSO solvent control group,12 rats in each group.We used chronic intermittent hypoxia to simulate the pathological and physiological changes of OSAS.The intermittent hypoxia was 8 hours per day,the hypoxia cycle was 3minutes,and the OSAS model rats were obtained after 4 weeks of modeling.Morris water maze(MWM)was used to observe the spatial learning and memory ability of SD rats.Hematoxylin-eosin(HE)staining was used to observe the tissue structure and neuronal morphology of hippocampal CA1 region.Immunohistochemistry staining was used to observe the expression site and intensity of P-STAT3(S727),the number and percentage of area of GFAP positive cells in hippocampal CA1 region of rats in each group.The expression of P-STAT3(S727)and GFAP protein in hippocampus of experimental rats was observed by Western Blot(WB).Results: The oxygen saturation of the tail artery in the OSAS rats was significantly lower than that in the reoxygenation phase(P<0.05).In the Morris water maze experiment,the escape latency of the OSAS model rats was longer than that of the control group(P<0.05).The escape latency shortened after the AG490 inhibitor was administered(P<0.05).There was no significant difference between DMSO group and OSAS group.The number of OSAS rats crossing the original escape platform was higher than that of the normal group(P<0.05).The number of the inhibitor group crossing the platform increased compared with that of the OSAS group(P<0.05).There was no significant difference in the DMSO group and the OSAS group.HE staining showed that the cells in the CA1 region of OSAS model not tightly arranged,the nucleus pyknosis,and the apoptosis increased.The CA1 region of the inhibitor group loose and structurally disordered,and the cell morphology irregular.Compared with the OSAS group,the apoptosis decreased.The pathological changes in the DMSO solvent group were comparable to those in the OSAS group.There was no significant difference in pathological changes between DMSO group and OSAS group.The expression of P-STAT3(S727)in hippocampal CA1 region of OSAS rats was higher than that in normal group(P<0.05).The expression of P-STAT3(S727)in the inhibitor group was lower than that in the OSAS group(P<0.05).There was no significant difference in the expression of P-STAT3(S727)between the DMSO group and the OSAS group.the number and percentage of area of GFAP positive cells in hippocampal CA1 region of OSAS model rats was higher than that of normal group(P<0.05).The number and percentage of area of GFAP-positive cells in AG490 group was less than that in OSAS group(P<0.05).There was no significant difference between DMSO group and OSAS group.The WB results showed that the expression of P-STAT3(S727)protein in the OSAS model group was higher than that in the normal group(P<0.05),and the expression of P-STAT3(S727)in the inhibitor group was lower than that in the model group(P<0.05).There was no significant difference between DMSO group and OSAS group.the expression of GFAP protein in OSAS model group was higher than that in normal group(P<0.05),and the expression of GFAP in inhibitor group was lower than that in model group(P<0.05).There was no significant difference between DMSO group and OSAS group.Conclusion: The cognitive dysfunction caused by OSAS may be related to the overexpression of GFAP in hippocampus,which may be the activation of JAK2/STAT3 signaling pathway.