Cui Min, Yang Wei-Ming, Yao Ping
Department of Gastroenterology, The First Affiliated Hospital of Xinjiang Medical University, No.137 LiYuShan Road Xinjiang Province, Urumqi, 830000, China.
Xinjiang Medical University, Xinjiang Province, Urumqi, 830000, China.
Sci Rep. 2025 Jan 22;15(1):2760. doi: 10.1038/s41598-025-86823-0.
Although low-dose lactulose has shown a good theoretical foundation for the treatment of ulcerative colitis (UC) in previous studies, the exact effects and mechanism remain unclear. The rats were randomly distributed into 5 groups, i.e., normal drinking water was provided for an initial 14 days in blank control group, 4% dextran sulfate sodium was used for modeling in the remaining 4 groups. During the 15-24th day, rats in the blank control group were administered with 0.9% saline (0.5 ml/d) by gavage. In the rest 4 groups, rats were administered 0.9% saline (0.5 ml/d, UC model), mesalazine (400 mg/kg/d), lactulose (1000 mg/kg/d), and lactulose + mesalazine (two-drug combination) by gavage. In addition to symptoms and pathological changes, serum IL-6, TNF-α, and High-sensitivity C-reactive protein(Hs-CRP) by ELISA analysis, mRNA and protein expression levels of TLR-2, TLR-4, Nuclear factor-κB(NF-κB), IL-6, and TNF-α in colon tissues by RT-qPCR and WB analyses respectively. Meanwhile, short-chain fatty acid(SCFAs) and intestinal flora were analyzed. Low-dose lactulose improved symptoms (diarrhea, blood in stool, weight loss) and pathological inflammation. In addition to serum IL-6, TNF-α, and Hs-CRP, the mRNA and protein expression levels of TLR-2, TLR-4, NF-κB, IL-6 and TNF-α in the colon were down-regulated with the intervention of lactulose.Meanwhile, lactulose decreased the ileocecal PH, increased SCFAs and altered the intestinal flora. Low-dose lactulose may be beneficial to UC by regulating TLRs/NF-κB pathway, reducing ileocecal PH, increasing SCFAs, regulating intestinal flora and improving the intestinal mucosal barrier. Meanwhile, low-dose lactulose and mesalazine may have additive effects upon combination.
尽管低剂量乳果糖在先前的研究中已显示出治疗溃疡性结肠炎（UC）的良好理论基础，但其确切效果和机制仍不清楚。将大鼠随机分为5组，即空白对照组最初14天提供正常饮用水，其余4组用4%葡聚糖硫酸钠进行造模。在第15至24天期间，空白对照组大鼠通过灌胃给予0.9%生理盐水（0.5 ml/d）。其余4组大鼠通过灌胃分别给予0.9%生理盐水（0.5 ml/d，UC模型组）、美沙拉嗪（400 mg/kg/d）、乳果糖（1000 mg/kg/d）以及乳果糖+美沙拉嗪（两药联合）。除了观察症状和病理变化外，通过ELISA分析血清白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和高敏C反应蛋白（Hs-CRP），分别通过RT-qPCR和WB分析结肠组织中Toll样受体2（TLR-2）、Toll样受体4（TLR-4）、核因子-κB（NF-κB）、IL-6和TNF-α的mRNA和蛋白表达水平。同时，分析短链脂肪酸（SCFAs）和肠道菌群。低剂量乳果糖改善了症状（腹泻、便血、体重减轻）和病理炎症。除血清IL-6、TNF-α和Hs-CRP外，结肠中TLR-2、TLR-4、NF-κB、IL-6和TNF-α的mRNA和蛋白表达水平在乳果糖干预下下调。同时，乳果糖降低了回盲部pH值，增加了SCFAs并改变了肠道菌群。低剂量乳果糖可能通过调节TLRs/NF-κB通路、降低回盲部pH值、增加SCFAs、调节肠道菌群和改善肠道黏膜屏障而对UC有益。同时，低剂量乳果糖与美沙拉嗪联合可能具有相加作用。
