目的 探究枸杞多糖（LBP）对慢性溃疡性结肠炎（UC）小鼠的治疗作用及机制。方法 将60只SPF级C57 BL/6小鼠随机分为对照组、模型组、柳氮磺吡啶肠溶片（阳性药，200 mg·kg^-1）组和LBP低、高剂量（40、160 mg·kg^-1）组，通过自由饮用2%的葡聚糖硫酸钠（DSS）建立慢性UC小鼠模型。通过疾病活动指数（DAI）评估小鼠慢性UC的疾病严重程度，测量结肠长度并计算结肠黏膜损伤指数（CMDI）判断结肠炎症程度。苏木精-伊红（HE）染色分析肠道黏膜的损伤状态；ELISA法检测结肠及血清样本中的肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β、IL-4、IL-10水平；采用非靶向代谢组学检测结肠组织内代谢水平的变化，结合京都基因与基因组百科全书（KEGG）数据库富集分析探究LBP治疗UC的潜在机制；Western blotting法测定证肠组织中芳烃受体（AHR）、Toll样受体（TLR4）和核因子-κB（NF-κB）p-p65的蛋白的表达水平。结果 与模型组相比，经LBP干预后的慢性UC小鼠的DAI和CMDI评分显著下降（P＜0.05、0.01），结肠长度显著增加（P＜0.05）；结肠黏膜损伤状态得到改善；促炎因子TNF-α和IL-1β表达水平明显降低，同时抗炎因子IL-4和IL-10表达水平明显升高（P＜0.05、0.01、0.001）；代谢组学结果表明，LBP显著上调164个代谢物，下调151个代谢物，色氨酸代谢等途径显著改变；Western blotting结果表明，LBP通过调控色氨酸代谢下游的AHR/TLR4/NF-κB信号通路缓解小鼠UC。结论 LBP通过改变色氨酸代谢，激活AHR受体，抑制TLR4/NF-κB通路，调节炎症因子水平，显著改善UC。

Objective To explore the therapeutic effect and mechanism of Lycium barbarum polysaccharides (LBP) on chronic ulcerative colitis (UC) in mice.Methods Sixty SPF-grade C57 BL/6 mice were randomly divided into the control group, model group, sulfasalazine enteric-coated tablets (positive drug, 200 mg·kg^-1) group, and LBP low-dose (40 mg·kg^-1) and high-dose (160 mg·kg^-1) groups. A chronic UC mouse model was established by free drinking of 2% dextran sulfate sodium (DSS). The disease activity index (DAI) was used to evaluate the severity of chronic UC in mice, and the colon length was measured and the colon mucosal damage index (CMDI) was calculated to determine the degree of colonic inflammation. Hematoxylin-eosin (HE) staining was used to analyze the damage state of intestinal mucosa; ELISA was used to detect the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-4, and IL-10 in colon and serum samples; non-targeted metabolomics was used to detect changes in the metabolic levels of colon tissue, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for enrichment analysis to explore the potential mechanism of LBP in treating colitis; Western blotting was used to detect the expression levels of aryl hydrocarbon receptor (AHR), Toll-like receptor (TLR4), and nuclear factor-κB (NF-κB) p-p65 proteins in intestinal tissue.Results Compared with the model group, the DAI and CMDI scores of chronic UC mice after LBP intervention were significantly decreased (P<0.05, 0.01), and the colon length was significantly increased (P<0.05); The damage state of colonic mucosa was improved; The expression levels of proinflammatory factors TNF-α and IL-1β were significantly decreased, while the expression levels of anti-inflammatory factors IL-4 and IL-10 were significantly increased (P<0.05, 0.01, 0.001); The metabolomics results showed that LBP significantly upregulated 164 metabolites and downregulated 151 metabolites, and the tryptophan metabolism pathway was significantly altered; The Western blotting results indicated that LBP alleviated colitis in mice by regulating the AHR/TLR4/NF-κB signaling pathway downstream of tryptophan metabolism.Conclusion LBP significantly ameliorated UC by altering tryptophan metabolism, activating the AHR, inhibiting the TLR4/NF-κB pathway, and modulating the levels of inflammatory factors, demonstrating its potential in the treatment of UC.

R285.5

常州市医学创新人才培养项目（KY201129）