Experimental study of ursolic acid regulating HMGB1/TLR4 pathway to reduce intestinal barrier injury in a rat model of ulcerative colitis
10.3969/j.issn.1000-484X.2025.03.019
- VernacularTitle:熊果酸调控HMGB1/TLR4通路减轻溃疡性结肠炎大鼠模型肠屏障损伤的实验研究
- Author:
Hongxin LI
1
;
Jing LIU
;
Zewen FAN
;
Wenbo XU
Author Information
1. 沧州市人民医院检验科,沧州 061000
- Publication Type:Journal Article
- Keywords:
Ursolic acid;
HMGB1/TLR4 pathway;
Ulcerative colitis;
Intestinal barrier injury
- From:
Chinese Journal of Immunology
2025;41(3):620-627
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the mechanism of ursolic acid regulating HMGB1/TLR4 pathway in reducing intestinal barrier injury in a rat model of ulcerative colitis(UC).Methods:Rats were randomly divided into control group,model group,glycyr-rhizic acid(HMGB1 inhibitor)group,ursolic acid group and glycyrrhizic acid+ursolic acid group,with 12 rats in each group.UC rat model was induced by tritrobenzene sulfonate enema.After drug administration,body weight and disease activity index(DAI)score were performed of rats in each group;pathological morphology of colonic mucosa was detected by HE staining,the thickness of mucosa and height of villi were compared;levels of catalase(CAT),superoxide dismutase(SOD),malondialdehyde(MDA)in colon tissue,levels of serum diamine oxidase(DAO),and intestinal fatty acid binding protein(I-FABP),TNF-α,IL-18,IL-6 were detected by kits;expression levels of tight junction proteins(Claudin-1,ZO-1,Occludin)and HMGB1/TLR4 pathway proteins(HMGB1,TLR4,MyD88)in colon tissues were detected by Western blotting.Expression levels of HMGB1,TLR4 and MyD88 in colonic tissue were detected by immunohistochemistry.Results:Compared with control group,colonic mucosal tissue of model group had severe pathological injury,the body weight,mucosal thickness,villus height,CAT,SOD,Claudin-1,ZO-1 and Occludin levels in colon tis-sue were significantly reduced,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly increased(P<0.05);compared with model group,pathological injury of colonic mucosal tissue of rats in ursolic acid group,glycyrrhizic acid group and glycyrrhizic acid+ursolic acid group were reduced,body weight,muco-sal thickness,villus height,colon tissue CAT,SOD,Claudin-1,ZO-1 and Occludin levels were significantly increased,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly reduced(P<0.05);combined intervention of glycyrrhizic acid and ursolic acid could enhance the influence of ursolic acid on the above indexes(P<0.05).Conclusion:Ursolic acid can inhibit inflammation,reduce the level of oxidative stress,reduce the colonic mucosal injury of UC rats,repair the intestinal mucosal barrier function,and improve the clinical symptoms of rats,which may be achieved by down-regulating the HMGB1/TLR4 pathway.
