杜仲叶多糖对慢性酒精性肝损伤小鼠的保护作用

Protective Effect of Eucommia ulmoides Oliv. Leaf Polysaccharides in Mice with Chronic Alcoholic Liver Injury

摘要:

为了探讨杜仲叶多糖（EULP）对慢性酒精性肝损伤小鼠的保护作用，该研究以56%vol北京红星二锅头灌胃9周建立小鼠慢性酒精中毒模型，并在建模后期给予EULP干预3周。采用苏木精-伊红（HE）染色观察小鼠肝脏、回肠组织形态，并测定肝脏组织白细胞介素1β（IL-1β）的含量。采集小鼠粪便进行肠道菌群测序，利用液相色谱-质谱（LC-MS）技术开展血清非靶代谢组学。体外结果表明，EULP质量浓度为1.6 mg/mL时，对DPPH、•OH及ABTS•+的清除率分别约为64.51%、80.15%和93.92%。动物实验表明，与模型组相比，EULP中、高剂量组肝脏中IL-1β表达水平显著降低约34.87%、39.93%，且能有效改善小鼠肝脏、肠道组织损伤程度。中剂量EULP干预后变形菌门和脱铁杆菌门丰度相比于模型组提高约112.48%、175.07%。代谢组学筛选出5个潜在血清生物标志物，并揭示EULP通过调控花生四烯酸代谢通路缓解肝脏损伤。综上，EULP可以调节肝损伤、炎症反应、肠道菌群及血清代谢，展现出治疗慢性酒精性肝损伤的潜力，为开发食源性多糖类解酒产品提供理论依据。

Abstract:

A chronic alcohol intoxication mouse model was established to determine the protective effects of Eucommia ulmoides Oliv. leaf polysaccharides (EULP) against chronic alcoholic liver injury in mice. The model was established by intragastric administration of 56% vol Beijing Hongxing Erguotou for 9 weeks, with EULP intervention administered via gavage for the final three weeks of modeling. Hematoxylin-eosin (HE) staining was used to observe the morphological changes in liver and ileum tissues, and the content of interleukin-1β (IL-1β) in liver tissues was determined. Fecal samples were collected from the mice for gut microbiota sequencing; serum non-targeted metabolomics was performed using liquid chromatography-mass spectrometry (LCMS). In vitro results indicated that when the mass concentration of EULP was 1.6 mg/mL, the scavenging rates for DPPH, •OH, and ABTS•+ were 64.51%, 80.15%, and 93.92%, respectively. In animal experiments, the expression level of IL-1β in the liver of the medium- and high-dose EULP groups was reduced by 34.87% and 39.93%, respectively, relative to the control, and the extent of injury in mouse liver and intestinal tissues was effectively improved. The abundances of Proteobacteria and Deferribacteres following medium-dose EULP intervention were increased by approximately 112.48% and 175.07%, respectively, compared to the model group. Five potential serum biomarkers were identified using metabolomics analysis, which indicated that liver injury was alleviated by EULP via regulation of the arachidonic acid metabolism pathway. Collectively, EULP was shown to regulate liver injury, inflammatory response, gut microbiota, and serum metabolism, demonstrating potential for the treatment of chronic alcoholic liver injury and providing a theoretical foundation for the development of food-derived, polysaccharide-based detoxification products.