Mechanism study on inhibition of ulcerative colitis by Sirt1 signaling axis mediated by oridonin
10.3969/j.issn.1000-484X.2024.07.019
- VernacularTitle:冬凌草甲素介导Sirt1信号轴抑制溃疡性结肠炎的机制研究
- Author:
Maonan WANG
1
;
Bo XU
;
Linyue LI
;
Shurong LI
;
Mingcheng LI
Author Information
1. 吉林省人民医院,长春 130012
- Keywords:
Oridonin;
Ulcerative colitis;
Sirt1 signaling pathway;
Inflammation factors
- From:
Chinese Journal of Immunology
2024;40(7):1461-1466
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To build mice ulcerative colitis(UC)model by dextran sodium sulfate salt(DSS),and to explore effect and molecular mechanism of oridonin(Ori)on alleviating UC by mediating Sirt1 signaling pathway,as well as to find new drugs for UC treatment.Methods:Sixty BALB/c mice were randomly divided into normal group(NC),model group(DSS),DSS+mesalazine sustained-release granule group(AC),DSS+low-dose Ori group(Ori-L),DSS+medium-dose Ori group(Ori-M)and DSS+high-dose Ori group(Ori-H),with 10 mice in each group.Except NC group,mice in other groups were given 3%DSS aqueous solution free for 7 days.After successful modeling,Ori-L group,Ori-M group and Ori-H group were intragastric with 50,100 and 150 mg/kg Ori suspension,respectively.NC group and DSS group drank distilled water free,AC group was intragastric with mesalazine sustained-release granules 100 mg/kg,lasted for 10 days.Weight changes of mice were recorded and disease active index(DAI)score was performed.After treatment,serum levels of IL-1β and tumor necrosis factor-α(TNF-α)were detected by ELISA.Whole colon tissues were extracted,length was measured,and HE staining was performed.Real-time fluorescence quantitative PCR and Western blot were used to detect expressions of Sirt1,NF-κB and p53 in colon tissues of each group.Results:After successful modeling,compared with NC group,the other 5 groups of mice showed weight loss,DAI score increased and colon length shortened,Sirt1 expression was signi-ficantly inhibited,while expressions of NF-κB and p53 were significantly increased,accompanied by obvious inflammatory pathologi-cal features.Compared with DSS group,Ori-L,Ori-M,and Ori-H groups and AC group had less weight loss during experiment,and DAI scores showed lower disease activity and relatively less colon length shortening,Sirt1 expression was less inhibited,expressions of NF-κB and p53 were also relatively small.Results of AC group could prove that Ori has therapeutic effect on UC.Conclusion:Ori can improve UC in mice,whose effect may be related to regulation of Sirt1 signal.
