Lraglutide improves postoperative cognitive function of aged mice via inhibiting the β-arrestin2/STING/TBK1 pathway
AIM:To investigate the effects and possible mechanisms of liraglutide on postopera-tive cognitive function in aged mice.METHODS:C57BL/6J male-aged mice were randomly divided into 4 groups:control group(N group),liraglutide group(L group),model group(M group),and mod-el+liraglutide group(ML group).There were 12 mice in each group.The model was constructed by using sevoflurane anesthesia combined with dis-secting the abdominal cavity in M and ML groups.In L and M groups,liraglutide was injected into the peritoneal cavity at 300 μg/kg,once per day,for 14 days.Postoperatively,the cognitive function of mice was detected by using the open field test,the Y maze experiment,and the conditioned fear ex-periment.Western blotting and ELISA were used to detect the expression of hippocampal glucagon-like peptide-1 receptor(GLP1R),β-arrestin2(β-arres-tin2),stimulator of interferon genes(STING),TANK-binding kinase 1(TBK1),IL-1β,and IL-6;immunoflu-orescence was used to observe the Iba1-positive microglial cell quantity.RESULTS:Compared with N group,M group showed a decrease in the postop-erative spontaneous alternation rate,percentage of freezing time,and GLP1R expression in hippocam-pal tissue(P＜0.05)and an increase in the expres-sion of β-arrestin2,STING,P-TBK1,IL-6,IL-1β,and the number of Iba1-positive cells(P＜0.05).Com-pared with M group,postoperative spontaneous al-ternation rate,percentage of freezing time,and GLP1R expression were increased in ML group(P＜0.05),and the number of β-arrestin2,P-TBK1,IL-6,IL-1β,and Iba1-positive cells was significantly de-creased in ML group(P＜0.05).CONCLUSION:Lira-glutide may ameliorate postoperative cognitive im-pairment in aged mice by inhibiting the β-arrestin2/STING/TBK1 pathway.
万方数据
维普
