Study The Effect Of High Altitude Hypoxia On Spleen Tissue Of Mice Based On Transcriptome Sequencing

Objective: The transcriptome sequencing technology was used to explore the molecular mechanism of the expression and response of the relevant genes in the immune system adaptation to high altitude hypoxia stress.Methods: In this study,C57BL/6 mice were reared at a high altitude of 4200meters(plateau hypoxic group,HST group)and 400 meters above sea altitude(plain normal oxygen group,PSC group),respectively,and the spleen tissue of the mice was sterilized for transcriptome sequencing using RNA-Seq after 30 days.The sequencing results of the HST group and the PSC group were analyzed for difference analysis and enrichment analysis,and the reliability of the sequencing results was verified by RT-q PCR experiments.In addition,14 genes associated with immune response,such as LCN2,S100A8,S100A8,S100A9,ELANE,CTSG,FCGR4,APOA1,APOA2,APOA4,RXRB,SCD3,ALOX15,HPGDS and PTGS2,were selected for RT-q PCR experiments,and LCN2,S100A8,S100A9,APOA1,APOA2,APOA4,ALOX15,HPGDS and PTGS2 were selected for Western Blot experiment.Results: Compared with the PSC group,1950 differential genes were up-regulated and 2268 differential genes were down-regulated in the HST group(P<0.05).The results of GO and KEGG analysis showed significant enrichment of the adaptive immune system and JAK-STAT and NOD-LIKE receptor signaling pathways.GSEA showed that the expression of differential gene sets of NOD-LIKE receptor signaling pathways in the plateau hypoxia group showed an upward trend.The results of RT-q PCR showed that compared with PSC group,the expression levels of DEGs related to IL-17 signaling pathway(LCN2,S100A8,S100A9),SLE(ELANE,CTSG,FCGR4)and AA metabolic pathway(ALOX15,HPGDS)in HST group were significantly increased.The expression levels of DEGs(APOA1 and APOA4)related to PPAR signaling pathway and cholesterol metabolism pathway decreased significantly.The results of Western Blot showed that compared with PSC group,the protein expression of LCN2,HPGDS and PTGS2 in HST group was enhanced.The protein expression of S100A8,S100A9,APOA1,APOA2,APOA4 and ALOX15 was inhibited.Conclusion: Plateau hypoxia stimulation may cause an imbalance of immune regulation and inflammatory response within the body by affecting inflammation-related pathways and lipid metabolic processes in the body.