Effection Research Of JAK2/STAT3 Regulating M1mAChR On Learning And Memory Ability Of OSAS Rats

Objective: JAK2/STAT3 pathway inhibitor AG490 and M1 mAChR agonist VU0364572,were used to observe the protective effect of M1 mAChR on the OSAS-induced cognitive impairment and the regulatory effect of JAK2/STAT3 pathway.Methods: 54 male SD rats were randomly divided into six groups: normal control group,OSAS model group(OSAS),OSAS with AG490 pretreatment group(AG490),OSAS with VU0364572 pretreatment group(VU0364572),OSAS with AG490+VU0364572pretreatment group(AG490+VU0364572)and dimethyl sulfoxide control group(DMSO).All five groups of rats except the normal control group were treated with chronic intermittent hypoxia to established the OSAS model.The drug intervention group was pretreated respectively with AG490,VU0364572,AG490+VU0364572 and DMSO during the modeling period.Morris water maze and HE staining were used to observe the behavioral and histopathological changes.Western blot was used to detect the changes of t-STAT3,p-STAT3 and M1 mAChR in the hippocampus of OSAS rats,and the effects of administration intervention on the expression of target protein in the hippocampus of OSAS rats were also compared.The localization of the target protein was observed by immunohistochemistry.Results: 1.Morris water maze: The escape latency in OSAS group and DMSO group was significantly longer than that in normal group(P < 0.05),and the number of times that crossing platform was significantly decreased(P < 0.05).However,there was no significant difference between AG490 group,AG490+VU0364572 group and DMSO group in escape latency and platform crossing times.The escape latency of VU0364572 group was shorter than that of DMSO group(P < 0.05),and the number of crossing platform was significantly increased(P < 0.05).2.HE staining: the hippocampal neurons in the normal control group were relatively orderly arranged,and the structure of the cells was clear.In OSAS group,AG490 group,AG490+VU0364572 group and DMSO group,the structure and morphology of hippocampal neurons were not clear,and the cytoplasm was heavily stained with eosin.Nuclear pyknosis appeared in some cells and the intercellular space was enlarged.Compared with the normal group,the cells of rats in VU0364572 group were slightly loosely arranged and a little necrosis,but lighter than the other four groups.3.Western blot: Compared with the normal control group,the contents of p-STAT3,t-STAT3 and M1 mAChR protein in the hippocampus of OSAS group decreased(P < 0.05),but there was no significant difference between the DMSO group and the control group.The contents of p-STAT3 and t-STAT3 in the hippocampus of rats in AG490 group,AG490+VU0364572 group and VU0364572 group were not significantly different from those in DMSO group(P < 0.05),while the content of M1 mAChR protein in the hippocampus of rats in VU0364572 group were higher than that in DMSO group(P <0.05).4.Immunohistochemistry: t-STAT3 positive staining in rat hippocampus was brownish yellow,mainly expressed in the cytoplasm of nerve cells.p-STAT3 positive staining was yellow,mainly expressed in the nucleus and cytoplasm of nerve cells.M1 mAChR positive staining was yellow,mainly expressed on the cell membrane of nerve cells.Conclusion: JAK2/STAT3 pathway plays a regulatory role in the improvement of cognitive ability of OSAS rats by M1 mAChR.