Effect of Midazolam on visceral pain in rats with diarrheal irritable bowel syndrome based on the FoxO1/FoxO3a pathway
10.13431/j.cnki.immunol.j.20250066
- VernacularTitle:基于FoxO1/FoxO3a通路分析咪达唑仑对腹泻型肠易激综合征大鼠内脏痛的影响
- Author:
Yu ZHANG
1
;
Mengjiao ZHAO
Author Information
1. 长安医院麻醉科,西安 710016
- Publication Type:Journal Article
- Keywords:
diarrheal irritable bowel syndrome;
forkhead box protein O1;
forkhead box transcription factor O3a;
Midazolam;
visceral pain
- From:
Immunological Journal
2025;41(7):454-460
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze the effect of Midazolam(MID)on visceral pain in diarrheal irritable bowel syndrome(IBS-D)rats based on the forkhead box protein O1/forkhead box transcription factor O3a(FoxO1/FoxO3a)pathway.Methods An IBS-D rat model was constructed,and successfully modeled rats were randomly assigned into IBS-D group,low MID(MID-L)group,high MID(MID-H)group,and MID-H+AS1842856 group,with 12 rats in each group.Additionally,12 normal healthy rats were included as the Control group.The Control group and the IBS-D group were intraperitoneally injected with an equal volume of 0.9%sodium chloride.The MID-L and MID-H groups were intraperitoneally injected with 30 and 90 mg/kg MID respectively,while the MID-H+AS1842856 group was intraperitoneally injected with 90 mg/kg MID and given 50 mg/kg AS1842856 by gavage.Rats in each group were evaluated for abdominal wall withdrawal response(AWR)score.Enzyme-linked immunosorbent assay(ELISA)was applied to detect the levels of oxidative stress and pain factors in serum,and HE staining was applied to detect pathological changes in colonic tissue.Immunohistochemistry was applied to detect the expression of glial fbrillary acidic protein(GFAP)and nerve growth factor(NGF)in colon tissue,and Western Blot method was applied to detect the expression of proteins related to the FoxO1/FoxO3a pathway.Results The pathological damage in the colonic tissue in the IBS-D group was more severe than that in the Control group,and the AWR score,malondialdehyde(MDA),substance P(SP),5-hydroxytryptamine(5-HT),and GFAP and NGF expression elevated,while the superoxide dismutase(SOD)level and the expression of FoxO1 and FoxO3a decreased(P<0.05).The colonic tissue damage in the MID-L and MID-H groups was less severe compared with the IBS-D group,and the AWR score,MDA,SP,5-HT,and GFAP and NGF expression decreased,while SOD level and the expression of FoxO1,FoxO3a increased;the changes were more significant in the MID-H group(P<0.05).The colonic tissue damage in the MID-H+AS1842856 group was more severe than that in the MID-H group,and the AWR score,MDA,SP,5-HT,and GFAP and NGF expression increased,while SOD level level and the expression of FoxO1,FoxO3a decreased(P<0.05).Conclusion MID can improve visceral pain in IBS-D rats,and its mechanism of action is related to the activation of the FoxO1/FoxO3a pathway.
