时珍国医国药2025,Vol.36Issue(23):4429-4435,7.DOI:10.70976/j.1008-0805.SZGYGY-2025-2304
安肠汤调控P2X7R/NF-κB/NLRP3/GSDMD通路对溃疡性结肠炎大鼠炎症和细胞焦亡的影响
Effects of Anchang Decoction(安肠汤)on inflammation and pyroptosis in ulcerative colitis rats via regulating the P2X7R/NF-κB/NLRP3/GSDMD pathway
摘要
Abstract
Objective To investigate the mechanism by which Anchang Decoction(安肠汤,ACD)alleviates inflammatory response and pyroptosis in rats with ulcerative colitis(UC)through regulating the P2X7R/NF-κB/NLRP3/GSDMD pathway.Methods Forty-eight Wistar rats were randomly divided into the following groups(n=8 per group):the control group,model group,Mesalazine group(0.42 g/kg),and ACD low/medium/high-dose groups(ACD-L,ACD-M,ACD-H;11.55,23.1,46.2 g/kg).The UC model was established using 2,4,6-trinitrobenzene sulfonic acid(TNBS).The general condition of rats,colonic mucosal damage index(CMDI)score,and colon length were evaluated.Intestinal pathology was observed by HE staining.Serum levels of IL-1β and IL-18 were measured using ELISA.The expressions of caspase-1 and GSDMD proteins in the colon were detected by immunohistochemistry(IHC).Protein expres‐sions of P2X7 receptor(P2X7R),NF-κB p65,p-NF-κB p65,NLRP3,C-caspase-1,and GSDMD N-terminal domain(GSDMD-N)in the colon were analyzed by Western blot(WB).The mRNA expressions of related genes were detected by real-time quantitative poly‐merase chain reaction(RT-qPCR).Results Compared with the control group,rats in the model group exhibited deteriorated general condition,elevated CMDI score,shortened colon length,and severe pathological damage.Serum levels of IL-1β and IL-18 were signifi‐cantly elevated.The IHC-positive areas for caspase-1 and GSDMD,as well as the protein and mRNA expression levels of P2X7R,p-NF-κB p65,NLRP3,C-caspase-1,and GSDMD-N were all significantly increased(P<0.01).Compared with the model group,rats in the Mesalazine group and all ACD dose groups showed improved general conditions,reduced CMDI score,increased colon length,ameliorated colonic mucosal structure,and decreased serum levels of IL-1β and IL-18.The relative IHC-positive areas for caspase-1 and GSDMD,as well as the expression levels of the aforementioned key proteins(P2X7R,p-NF-κB p65,NLRP3,C-caspase-1,GSDMD-N)and their corresponding mRNAs,were significantly reduced(P<0.05 or P<0.01).Conclusion ACD may alleviate intes‐tinal inflammation and pyroptosis in UC rats by inhibiting the P2X7R/NF-κB/NLRP3/GSDMD signaling axis.关键词
安肠汤/P2X7R/NF-κB/NLRP3/GSDMD通路/溃疡性结肠炎/细胞焦亡Key words
Anchang Decoction(安肠汤)/P2X7R/NF-κB/NLRP3/GSDMD pathway/Ulcerative colitis/Pyroptosis分类
医药卫生引用本文复制引用
段晓鑫,黄深,杨桃,文亦磊,周艳,刘嘉琪,孙平良..安肠汤调控P2X7R/NF-κB/NLRP3/GSDMD通路对溃疡性结肠炎大鼠炎症和细胞焦亡的影响[J].时珍国医国药,2025,36(23):4429-4435,7.基金项目
国家自然科学基金项目(82160906,82160880) (82160906,82160880)
广西中医药大学桂派杏林拔尖人才资助项目(2022C020) (2022C020)
广西中医药大学研究生教育创新计划项目(YCBXJ2023012) (YCBXJ2023012)