Exploring the effect of intranasal insulin on hippocampal mRNA expression profile in mice with postoperative delirium based on high-throughput sequencing technology
Objective To explore the target and signaling pathway of intranasal insulin on postoperative delirium(POD)mice by ap-plying mRNA high-throughput sequencing technology.Methods Eighteen female and C57BL/6J mice were randomly divided into control group(group C),operation group(group N)and insulin group(group I),with 6 mice in each group.Group C and group N were given intranasal saline for 4 days,group I was given intranasal insulin for 4 days,30 minutes after the 4th day of administration,group N and group I were given exploratory laparotomy under 1.4%isoflurane,group C did not receive surgery.Open field experiment was conducted 4 hours after surgery/anesthesia to test the cognitive function of mice,and then the mice were killed with neck ampu-tion.The hippocampus tissues of mice were collected for high-throughput sequencing to screen out the differentially expressed genes,and the differentially expressed genes were analyzed by GO and KEGG pathway enrichment.The sequencing results were verified by RT-qPCR.Results Compared with group N,420 differentially expressed genes in group I were significantly changed,among which 176 differentially expressed genes were up-regulated and 244 differentially expressed genes were down-regulated.The results of GO a-nalysis showed that the main enriched biological processes included metabolic processes,stress response,signal transduction,etc.It was mainly expressed in extracellular region,cell membrane and endoplasmic reticulum.The biological functions mainly involved ion bind-ing and REDOX enzyme activity.Enrichment analysis of KEGG pathway suggested that the pathway was mainly enriched in comple-ment and coagulation cascade,steroid hormone biosynthesis,PPAR,PI3K-AKT and other signaling pathways.Based on the above re-sults and combined with RT-qPCR validation,six key genes of Cyp2e1,Plg,Bhmt,Ereg,Cdhr5 and Pck1 were screened.Conclusion Intranasal insulin plays an important role in learning,memory and cognitive function by influencing inflammatory response,apoptosis,synaptic plasticity and neurotransmitter transmission through complement and coagulation cascade reaction,steroid biosynthesis,PPAR,PI3K/AKT and other signaling pathways.
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