目的 基于肠道菌群代谢探讨黄精生品多糖（polysaccharides from crude Polygonatum sibiricum，PSPC）及黄精酒制品多糖（polysaccharides from wine processed Polygonatum sibiricum，PSPW）对酒精性肝病（alcoholic liver disease，ALD）小鼠的影响及作用机制。方法 70只小鼠随机分为对照组、模型组、联苯双酯（100 mg/kg）组及PSPC高、低剂量（600、150 mg/kg）组和PSPW高、低剂量（600、150 mg/kg）组，每组10只。给予药物干预8周，每日给药4 h后，除对照组外，其余各组ig 40%红星二锅头白酒（15 mL/kg）建立ALD小鼠模型。分析各组小鼠体质量和肝脏指数变化；采用苏木素-伊红（hematoxylin-eosin staining，HE）染色观察肝脏组织病理学变化；检测血清中丙氨酸氨基转移酶（alanine aminotransferase，ALT）、天冬氨酸氨基转移酶（aspartate aminotransferase，AST）活性及三酰甘油（triglyceride，TG）、总胆固醇（total cholesterol，TC）含量、低密度脂蛋白胆固醇（low density lipoprotein cholesterol，LDL-C）水平；检测肝脏中过氧化氢酶（catalase，CAT）活性及丙二醛（malondialdehyde，MDA）水平；采用气相色谱法检测各组小鼠肠道内容物中短链脂肪酸（short chain fatty acids，SCFAs）含量；采用16S rRNA扩增子测序技术探讨黄精多糖对ALD小鼠肠道菌群的调节作用，分析肠道微生物群与各生化指标、SCFAs之间的相关性，预测相关功能性菌群。结果 与模型组比较，PSPC和PSPW均可提高ALD小鼠体质量，显著降低肝脏指数（P＜0.05），显著降低ALD小鼠血清中ALT、AST活性及TG、TC、LDL-C水平和肝组织中MDA水平（P＜0.05、0.01），并显著提高肝组织中CAT活性（P＜0.05、0.01）。肠道菌群及代谢产物结果表明，PSPC及PSPW可显著提高ALD小鼠肠道内容物中乙酸、丙酸、异丁酸、丁酸、异戊酸及戊酸6种SCFAs水平（P＜0.05、0.01），改善小鼠肠道菌群失调，其中对乳酸菌属、肠杆菌属、螺杆菌属、毛梭菌属、unclassified_f_Lachnospiraceae及Tuzzerella的异常有回调作用，以PSPW高剂量组调节作用最为明显。相关性分析结果表明ALT、AST、TG、TC、CAT及体质量与ALD小鼠菌群整体水平呈正相关，而LDL-C、MDA及6种SCFAs与ALD小鼠菌群整体水平呈负相关。结论 PSPC和PSPW均可有效保护酒精导致的肝损伤，并通过调节肠道菌群组成及代谢产物改善肝损伤，其中PSPW保护作用更强。

Objective To explore the effects and mechanisms of polysaccharides from crude Polygonatum sibiricum (PSPC) and polysaccharides from wine processed Polygonatum sibiricum (PSPW) on alcoholic liver disease (ALD) in mice based on gut microbiota metabolism. Methods A total of 70 mice were randomly divided into control group, model group, biphenyl diester (100 mg/kg) group, PSPC high- and low-dose (600, 150 mg/kg) groups, PSPW high-and low-dose (600, 150 mg/kg) groups, with 10 mice in each group. After eight weeks of drug intervention and 4 h of daily administration, except the control group, other groups were given 40% Hongxing Erguotou Baijiu (15 mL/kg) to establish ALD mouse model. Changes in body weight and liver index of mice in each group were analyzed; Hematoxylin- eosin staining (HE) was used to observe pathological changes in liver tissue; The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as well as levels of triglycerides (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in serum were detected; The activity of catalase (CAT) and level of malondialdehyde (MDA) in liver were detected; Gas chromatography was used to detect the contents of short chain fatty acids (SCFAs) in intestinal contents of mice in each group; The regulatory effect of P. sibiricum polysaccharides on gut microbiota of ALD mice was explored using 16S rRNA amplicon sequencing technology, the correlation between gut microbiota and various biochemical indicators, SCFAs were analyzed to predict the relevant functional microbiota. Results Compared with model group, both PSPC and PSPW could improve the body weight of ALD mice, significantly reduce liver index (P < 0.05), significantly reduce activities of ALT, AST and levels of TG, TC, LDL-C in serum and MDA level in liver tissue of ALD mice (P < 0.05, 0.01), and significantly increase CAT activity in liver tissue (P < 0.05, 0.01). The results of gut microbiota and metabolites showed that PSPC and PSPW significantly increased the levels of six SCFAs (acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid and valeric acid) in intestinal contents of ALD mice (P < 0.05, 0.01), and improved the imbalance of gut microbiota in mice. Among them, PSPC and PSPW had a regulatory effect on the abnormalities of Lactobacillus, Clostridium, Helicobacter, unclassified_f_Lachnospiraceae and Tuzzerella, with the high-dose PSPW group showing the most significant regulatory effect. The correlation analysis results showed that ALT, AST, TG, TC, CAT and body weight were positively correlated with the overall level of microbiota in ALD mice, while LDL-C, MDA and six SCFAs were negatively correlated with the overall level of microbiota in ALD mice. Conclusion Both PSPC and PSPW could effectively protect against alcohol induced liver injury, and improve liver injury by regulating gut microbiota composition and metabolic products, with PSPW having a stronger protective effect

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国家自然科学基金项目（82304727）；国家中医药管理局科技专项（GZY-KJS-2023-036）；国家中医药管理局全国老药工传承工作室（[2024]255号）；陕西省重点研发计划项目（2024SF-YBXM-460）；陕西省中医药管理局项目（SZY-KJCYC-2023-027，TZKN-CXRC-12）；“秦药”研发重点实验室（2021-QYPT-001）；陕西省卫生健康委秦药质量控制与创新产品研发创新团队