Effects and potential mechanisms of intestinal microbiota-mediated synthesis of neurotransmitter 5-hydroxytryptamine on radiation enteritis
Objective:To explore the effect of neurotransmitter 5-hydroxytryptamine(5-HT)on radiation enteritis and its mechanism.Methods:RNA sequencing was performed on intestinal tissues from control and irradiated wild-type(WT)mice to analyze transcriptome changes,and qRT-PCR was performed to verify the selected expression changes of genes.The level of 5-HT in control and irradiated intestinal tissues of WT mice was detected by immunofluorescence.Wild-type(WT)mice and tryptophan hydroxylase 1(Tph1)knockout(Tph1-/-)mice were both treated with radiotherapy,and the intestinal tissues of mice were performed with HE staining and Ki67 immunohistochemistry staining to compare the degree of intestinal tissue damage between them.RNA sequencing was performed on intestinal tissues from WT irradiation group and Tph1-/-irradiation group to analyze transcriptome changes.After antibacterial and antifungal treatment,WT mice were treated with irradiation,immunofluorescence was performed to detect the level of 5-HT in intestinal tissues.Meanwhile,HE staining and Ki67 staining were conducted.MDA and GSH/GSSG of intestinal tissues were detected.Results:The expression of Tph1 mRNA in intestinal tissues from WT mice was significantly increased,and the level of 5-HT was increased after irradiation.The intestinal tissues of WT mice were obviously damaged after irradiation,while the intestinal damage was relatively reduced after Tph1 knockout.Compared with WT irradiation group,the ferroptosis-promoting genes were significantly down-regulated and ferroptosis-inhibiting genes were significantly up-regulated in the intestinal tissues of Tph1-/-irradiation mice.MDA was decreased and GSH/GSSG was increased in Tph1-/-irradiation group.After antibacterial and antifungal treatment,the level of 5-HT in intestinal tissues of WT mice treated with irradiation was decreased,and the damage of irradiated intestinal tissues was alleviated to a certain extent.At the same time,MDA was decreased,and GSH/GSSG was increased.Conclusion:The intestinal flora can increase the level of 5-HT,potentially aggravating intestinal tissue injury after irradiation,in which ferroptosis may be involved.
万方数据
维普
