中药药理与临床2025，Vol.41Issue(8)：45-51,7.
异荭草苷调控NF-κB/NLRP3信号通路治疗溃疡性结肠炎
Isoorientin Regulates the NF-κB/NLRP3 Signaling Pathway for the Treatment of Ulcerative Colitis
摘要
Abstract
Objective:To observe the effects of isoorientin on the nuclear factor kappa B(NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway and intestinal barrier damage in mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS),and to explore its therapeutic effects and mechanisms in UC.Methods:Forty-eight C57BL/6J mice were randomly divided into six groups:a normal control group,a model control group,a mesalazine 600 mg/kg group,and isoorientin 25 and 50 mg/kg groups,and a 50 mg/kg isoorientin control group,with 8 mice in each group.Except for the normal control and isoorientin control groups,the remaining groups were administered 2%DSS solution for free drinking to establish the chronic UC mouse model.After 3 weeks,each drug-administered group received the corresponding treatment by gavage for 4 weeks.During the experiment,the general condition of the mice was observed,body weight changes were recorded,and the disease activity index(DAI)score was calculated.After drug administration,the mice were weighed,blood was collected via eyeball puncture,and colon tissue was dissected.Histopathological changes in colon tissue were observed u-sing hematoxylin-eosin(HE)and Alcian blue-periodic acid-Schiff(AB-PAS)staining.Serum levels of interleukin-6(IL-6),IL-8,IL-1β,tumor necrosis factor-α(TNF-α),IL-10,lipopolysaccharide(LPS),and myeloperoxidase(MPO)activity were detected by enzyme-linked immunosorbent assay(ELISA).The ultrastructure of colon tissue was observed by transmission electron microscopy.The expression of MUC2 in colon tissue was detected by immunofluorescence,and the expression of Occludin and ZO-1 was detected by immunohistochemistry.The protein levels of NF-κB,NLRP3,ASC,caspase-1,IL-18,and IL-1β in colon tissue were measured by Western blot.Results:Compared with the normal control group,the model control group showed significantly increased DAI scores,decreased body weight,shortened colon length,and increased intestinal weight index(P<0.01).Histological analysis revealed colonic mucosal destruction,inflammatory cell infiltration,and a significant reduction in goblet cells.Serum levels of IL-6,IL-8,IL-1β,TNF-α,LPS,and MPO activity were elevated,while IL-10 levels were decreased(P<0.01).The fluorescence intensity of MUC2 protein in colon tissue was significantly reduced,and the positive expression levels of Occludin and ZO-1 were decreased(P<0.05).The protein expression levels of p-NF-κB,NLRP3,ASC,caspase-1,IL-18,and IL-1β were significantly upregulated(P<0.01).In the isoorientin-treated groups(25 mg/kg and 50 mg/kg),DAI scores were significantly decreased,body weight increased,colon length was restored,and the intestinal weight index decreased(P<0.01).The structure of the intestinal mucosa improved,with regular arrangement of epithelial cells and an increase in goblet cells.Serum levels of IL-6,IL-8,IL-1β,TNF-α,LPS,and MPO activity were reduced,while IL-10 levels increased(P<0.01).The fluorescence intensity of MUC2 protein in colon tissue was signifi-cantly increased,and the positive expression levels of Occludin and ZO-1 were upregulated(P<0.05 or P<0.01).The protein expression levels of p-NF-κB,NLRP3,ASC,caspase-1,IL-18,and IL-1β were significantly downregulated(P<0.05 or P<0.01).Conclusion:Isoorien-tin has a good therapeutic effect on DSS-induced UC in mice.Its mechanism may be related to the inhibition of the NF-κB/NLRP3 signaling pathway and the protection of the intestinal mucosal barrier.关键词
异荭草苷/溃疡性结肠炎/核因子-κB/核苷酸结合寡聚化结构域样受体蛋白3信号通路/炎症反应/肠黏膜屏障Key words
Isoorientin/Ulcerative colitis/Nuclear factor kappa B/nucleotide-binding oligomerization domain-like receptor protein 3 signaling pathway/Inflammatory response/Intestinal mucosal barrier引用本文复制引用
高雅,陈健,张誉方,李丹彤,顾颖,李丽,张一昕..异荭草苷调控NF-κB/NLRP3信号通路治疗溃疡性结肠炎[J].中药药理与临床,2025,41(8):45-51,7.基金项目
国家自然科学基金青年基金项目(编号:82003913) （编号:82003913）
河北中医学院2022年燕赵医学研究项目(编号:YZZZ2022001). （编号:YZZZ2022001）
