中药药理与临床2025，Vol.41Issue(11)：51-57,7.
肠安方通过cGAS/STING通路介导肠上皮细胞焦亡缓解溃疡性结肠炎小鼠肠道炎症的机制研究
Chang'an Decoction Alleviates Intestinal Inflammation in Mouse Model of Ulcerative Colitis by Regulating cGAS/STING Pathway-Mediated Pyroptosis of Intestinal Epithelial Cells
摘要
Abstract
Objective:To explore the therapeutic mechanism of Chang'an(肠安)Decoction for ulcerative colitis in mice based on cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon response cGAMP interactor 1(STING)signaling path-way-mediated pyroptosis of intestinal epithelial cells.Methods:Forty-eight C57BL/6 mice were randomized into normal control,model con-trol,Chang'an Decoction(5,10,and 20 g/kg),and 5-amino salicylic acid(0.1 g/kg)groups.The mice in the normal control group re-ceived normal saline,and those in other groups had free access to 2％dextran sulfate sodium(DSS)solution for 7 days for the modeling of a-cute ulcerative colitis.After successful modeling,mice in each group were administrated with corresponding drugs by gavage,and the drug in-tervention was carried out for 5 days.During the experiment,the body weight,blood in stool,and disease activity index(DAI)were observed and recorded.At the end of the experiment,hematoxylin-eosin staining was conducted to reveal the histopathological changes in the colon tis-sue.Enzyme-linked immunosorbent assay was employed to assess the serum levels of interleukin-1β(IL-1β)and interleukin-18(IL-18).RT-qPCR was employed to determine the mRNA levels of Sting,NOD-like receptor thermal protein domain-associated protein 3(Nlrp3),gas-dermin D(Gsdmd),and cysteinyl aspartate-specific proteinase-1(Caspase1)in the colon tissue of mice in each group.Immunohistochemis-try was used to detect the expression of STING in mouse colon tissue.Immunofluorescence was used to detect the expression of GSDMD in mouse colon tissue.Western blotting was adopted to determine the protein levels of factors associated with the cGAS/STING pathway and py-roptosis in the colon tissue.Results:Compared with the normal control group,the model control group showed blood and bloody mucous in stools,weight loss(P<0.01),shortening of colon length(P<0.01),and elevated levels of IL-1β and IL-18(P<0.01).Pathological scores of the colon tissue suggested significant infiltration of inflammatory cells and inflammatory edema in the model control group.In addition,the colon tissue in the model control group showed up-regulated mRNA levels of Sting,Nlrp3,Caspase1,and Gsdmd(P<0.01),increased posi-tive expression of STING and GSDMD(P<0.01),and up-regulated protein levels of factors associated with the cGAS/STING pathway and pyroptosis(P<0.01).Compared with the model control group,Chang'an Decoction alleviated the bloody mucous in stools and weight loss(P<0.01),decreased the pathological scores,reduced the inflammatory infiltration of colonic cells(P<0.01),lowered the serum levels of IL-1β and IL-18(P<0.01),weakened the positive expression of STING and GSDMD(P<0.01),and down-regulated the mRNA levels of Sting,Nlrp3,Caspase1,and Gsdmd(P<0.01)and the protein levels of factors associated with the cGAS/STING pathway and pyroptosis in the colon tissue(P<0.01).Conclusion:Chang'an Decoction can reduce the expression of inflammatory factors and repair mucosal inflammation in the mouse model of ulcerative colitis by inhibiting the cGAS/STING signaling pathway-mediated pyroptosis of colonic epithelial cells.关键词
肠安方/溃疡性结肠炎/环磷酸鸟苷/腺苷酸合成酶/干扰素基因刺激因子信号通路/焦亡/黏膜炎症Key words
Chang'an Decoction/Ulcerative colitis/Cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)/stimulator of interferon response cGAMP interactor 1(STING)signaling pathway/Pyroptosis/Mucosal inflammation引用本文复制引用
金婷,汪颖琦,詹群璋,梁依敏,何龙,庄昆海,李培武,米红,刘凤斌..肠安方通过cGAS/STING通路介导肠上皮细胞焦亡缓解溃疡性结肠炎小鼠肠道炎症的机制研究[J].中药药理与临床,2025,41(11):51-57,7.基金项目
国家自然科学基金项目(编号:8190140285、82404958、82304982、8200151442) （编号:8190140285、82404958、82304982、8200151442）
国家中医药管理局第七批全国老中医药专家学术经验继承工作——刘凤斌广东省名中医传承工作室 （）
广东省基础与应用基础研究基金项目(编号:2023A1515110802). （编号:2023A1515110802）
