目的 探究枸杞多糖（LBP）對慢性潰瘍性結(jié)腸炎（UC）小鼠的治療作用及機(jī)制。方法 將60只SPF級C57 BL/6小鼠隨機(jī)分為對照組、模型組、柳氮磺吡啶腸溶片（陽性藥，200 mg·kg^-1）組和LBP低、高劑量（40、160 mg·kg^-1）組，通過自由飲用2%的葡聚糖硫酸鈉（DSS）建立慢性UC小鼠模型。通過疾病活動指數(shù)（DAI）評估小鼠慢性UC的疾病嚴(yán)重程度，測量結(jié)腸長度并計算結(jié)腸黏膜損傷指數(shù)（CMDI）判斷結(jié)腸炎癥程度。蘇木精-伊紅（HE）染色分析腸道黏膜的損傷狀態(tài)；ELISA法檢測結(jié)腸及血清樣本中的腫瘤壞死因子（TNF）-α、白細(xì)胞介素（IL）-1β、IL-4、IL-10水平；采用非靶向代謝組學(xué)檢測結(jié)腸組織內(nèi)代謝水平的變化，結(jié)合京都基因與基因組百科全書（KEGG）數(shù)據(jù)庫富集分析探究LBP治療UC的潛在機(jī)制；Western blotting法測定證腸組織中芳烴受體（AHR）、Toll樣受體（TLR4）和核因子-κB（NF-κB）p-p65的蛋白的表達(dá)水平。結(jié)果 與模型組相比，經(jīng)LBP干預(yù)后的慢性UC小鼠的DAI和CMDI評分顯著下降（P＜0.05、0.01），結(jié)腸長度顯著增加（P＜0.05）；結(jié)腸黏膜損傷狀態(tài)得到改善；促炎因子TNF-α和IL-1β表達(dá)水平明顯降低，同時抗炎因子IL-4和IL-10表達(dá)水平明顯升高（P＜0.05、0.01、0.001）；代謝組學(xué)結(jié)果表明，LBP顯著上調(diào)164個代謝物，下調(diào)151個代謝物，色氨酸代謝等途徑顯著改變；Western blotting結(jié)果表明，LBP通過調(diào)控色氨酸代謝下游的AHR/TLR4/NF-κB信號通路緩解小鼠UC。結(jié)論 LBP通過改變色氨酸代謝，激活A(yù)HR受體，抑制TLR4/NF-κB通路，調(diào)節(jié)炎癥因子水平，顯著改善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

常州市醫(yī)學(xué)創(chuàng)新人才培養(yǎng)項(xiàng)目（KY201129）