中国病理生理杂志2026，Vol.42Issue(5)：985-996,12.DOI:10.3969/j.issn.1000-4718.2026.05.016
肉苁蓉多糖通过抑制TLR4/NF-κB通路减轻小鼠肠道动力障碍相关溃疡性结肠炎
Cistanche deserticola polysaccharides attenuate ulcerative colitis associated with intestinal motility dysfunction in mice by inhibiting TLR4/NF-κB signaling pathway
摘要
Abstract
AIM:To investigate the effects and underlying mechanisms of Cistanche deserticola polysaccha-rides(CDPs)on ulcerative colitis(UC)associated with intestinal motility dysfunction induced by loperamide combined with dextran sulfate sodium in mice.METHODS:(1)A mouse model of UC associated with intestinal motility dysfunc-tion was established to evaluate the therapeutic effects of CDPs.Animals were divided into a normal control group,model group,positive control(5-aminosalicylic acid,100 mg/kg)group,low-dose(100 mg/kg)CDPs group,and high-dose(400 mg/kg)CDPs group.Histological staining was used to assess pathological changes in colonic tissues.To evaluate the efficacy of CDPs on intestinal motility,inflammation,and mucosal barrier integrity,we utilized a UC mouse model with motility dysfunction.The underlying molecular alterations were then analyzed via immunohistochemistry,immunofluores-cence,RT-qPCR and Western blot.(2)Fecal 16S rRNA sequencing combined with colon tissue transcriptomic sequenc-ing was conducted to analyze changes in gut microbiota abundance,differentially expressed genes,and key pathways be-tween the model and H-CDPs groups.(3)The human colonic epithelial cell line Caco-2 was used to verify the effects of CDPs on downstream signaling pathways.RESULTS:(1)Relative to the control group,model mice displayed severe dis-ease phenotypes,including profound body weight loss and elevated disease activity index scores.Additionally,macroscop-ic examination revealed a significant reduction in colorectal length(P<0.01).The number of CD11b-positive cells was significantly increased(P<0.01),the levels of inflammatory cytokines(interleukin-6,interleukin-1β and tumor necrosis factor-α)were significantly elevated(P<0.01),and the expression of E-cadherin and mucin 2 was significantly reduced(P<0.01).Compared with the model group,these indicators were significantly improved after CDPs treatment(P<0.05).(2)Compared with the model group,the high-dose CDPs group showed reduced abundance of harmful bacteria such as Enterobacter and Rikenellaceae_RC9_gut_group,increased abundance of beneficial bacteria such as Lactobacillus and Ligilactobacillus,and enhanced microbial diversity.Additionally,inflammation-related differentially expressed genes were significantly downregulated,mainly enriched in the nuclear factor-κB(NF-κB)signaling pathway.(3)Treatment with CDPs inhibited the expression of Toll-like receptor 4(TLR4)and the phosphorylation of NF-κB p65 and inhibitor of NF-κB α in lipopolysaccharide-induced Caco-2 cells,significantly down-regulated inflammatory cytokines,and up-regu-lated the expression of barrier-related genes.CONCLUSION:Treatment with CDPs can alleviate intestinal motility disor-ders and effectively attenuate UC by inhibiting the TLR4/NF-κB signaling pathway.关键词
肉苁蓉多糖/溃疡性结肠炎/肠道动力/TLR4/NF-κB信号通路Key words
Cistanche deserticola polysaccharides/ulcerative colitis/intestinal motility/TLR4/NF-κB signaling pathway分类
医药卫生引用本文复制引用
张雪红,范尚昊,王佳敏,蔡瑞,张迪,聂苏,张珂珂,陈开运..肉苁蓉多糖通过抑制TLR4/NF-κB通路减轻小鼠肠道动力障碍相关溃疡性结肠炎[J].中国病理生理杂志,2026,42(5):985-996,12.基金项目
广东省基础与应用基础研究基金资助项目(No.2023A1515220212) （No.2023A1515220212）
花都区基础与应用基础研究区院联合资助项目(No.23HDQYLH19) （No.23HDQYLH19）
