Immunological Journal 2025;41(3):129-137
doi:10.13431/j.cnki.immunol.j.20250019
TubA suppresses ferroptosis and ameliorates ulcerative colitis
Haixia CHEN 1 ; Minjia CHEN ; Jingqi SONG ; Ruixia HE ; Jing LIU ; Xiuqin CAO ; Zhiwei YANG
Affiliations
Keywords
HDAC6; Ulcerative colitis; Ferroptosis; TubA
Country
China
Language
Chinese
Abstract
Objective To explore the mechanism of TubA in the treatment of ulcerative colitis in mice,and to lay a foundation for the treatment strategy of ulcerative colitis.Methods Twenty C57BL/6 mice aged 6-8 weeks were randomly divided into 4 groups(n=5):the control group drank pure water every day,the model group and the treatment groups drank 3%dextran sulfate sodium(DSS)every day,and the treatment groups were injected with 10 mg/kg TubA and 20 mg/kg TubA every day from the third day,respectively.The weight changes of mice in all groups were recorded.Nine days later,the serum of mice was collected,and the expression levels of inflammatory factors IL-1β,IL-6 and IL-10 in serum were detected by ELISA.HE staining was used to observe the pathological changes of the mouse colon.The expression of myeloperoxidase(MPO)was detected by immunohistochemistry,the mRNA levels of inflammatory factors IL-1β,IL-6 and IL-10 were detected by RT-qPCR,and the expressions of GPX4 and FTH were detected by immunohistochemistry.The mRNA and protein expression levels of GPX4,GCLM,FTH,Nrf2,Keap1 and HO-1 in colon tissues were detected by RT-qPCR and Western blotting.Results Compared with the control group,the body weight and colon length of the model group decreased significantly.HE staining showed that inflammatory cells infiltrated the mucosa and submucosa of colon tissue,goblet cells were lost and crypt structure disordered and disappeared.Immunohistochemistry showed that the expression of MPO and FTH proteins were significantly increased,while the expression of GPX4 protein was significantly decreased(P<0.05).The mRNA and protein expression levels of IL-1β and IL-6 were significantly increased,while the mRNA and protein expression levels of IL-10 were significantly decreased(P<0.05).The mRNA and protein expression levels of FTH,Nrf2 and HO-1 were significantly increased,while the mRNA and protein expression levels of GPX4,GCLM and Keap1 were significantly decreased(P<0.05).After TubA treatment,compared with the model group,all these changes mentioned above suppressed(P<0.05).Conclusion TubA may reduce ulcerative colitis symptoms by inhibiting ferroptosis,providing new ideas for the treatment of ulcerative colitis.
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