目的:探讨二甲双胍对非酒精性脂肪性肝病(NAFLD)大鼠肠道菌群的影响。方法:雄性Sprague Dawley大鼠24只，适应性喂养2周后，将其分为健康对照组、NAFLD组和二甲双胍治疗组，每组8只。采用高脂饮食诱导建立NAFLD大鼠模型。采集血液标本检测各组ALT、AST、总胆固醇和三酰甘油水平。采用H-E和油红O染色观察肝脏组织病理学变化。根据操作分类单元聚类信息对大鼠肠道菌群结构进行α多样性分析(Chao指数和Shannon指数等)和主坐标分析(PCoA)。采用n t检验、单因素方差分析、秩和检验进行统计学分析。n 结果:二甲双胍治疗组大鼠血清ALT、AST、总胆固醇和三酰甘油水平均低于NAFLD组[分别为(58.43±4.89) U/L比(80.14±4.18) U/L、(160.14±13.04) U/L比(203.29±15.11) U/L、(1.534±0.113) mmol/L比(2.003±0.180) mmol/L、(0.724±0.105) mmol/L比(1.030±0.149) mmol/L]，差异均有统计学意义(n t＝-8.926、-5.719、-5.828、-4.446，n P均<0.05)。H-E和油红O染色结果显示，二甲双胍治疗后大鼠肝细胞排列较整齐，肝细胞肿胀程度较NAFLD组减轻，脂肪空泡数量减少，肝细胞红染明显减轻，脂滴数量减少，脂滴体积小且分布不均匀。二甲双胍治疗组Chao指数和Shannon指数均低于NAFLD组[690(668，703)比722(683，743)和4.16(4.09，4.42)比4.40(4.20，4.53)]，差异均有统计学意义(n Z＝-2.106、-2.083，n P均<0.05)。PCoA结果表明，NAFLD组和二甲双胍治疗组间的整体群落组成不同。在门水平，NAFLD组大鼠肠道菌群中厚壁菌门、变形菌门、放线菌门丰度均高于健康对照组(54.7%比45.5%、3.5%比2.1%、0.2%比0.1%)，而拟杆菌门、柔膜菌门丰度均低于健康对照组(41.3%比51.9%、9.4×10n -7比2.7×10n -3)，差异均有统计学意义(n Z＝-2.866、-2.726、-2.351、-2.901、-4.881，n P均<0.05)。在属水平，与健康对照组相比，NAFLD组丰度增加的菌属主要有布劳特氏菌属、拟杆菌属、罗斯氏菌属(0.6%比11.8%、0.9%比6.5%、1.1%比7.1%)，而普氏菌属、未分类的紫单胞菌属、未分类的瘤胃球菌属、乳酸杆菌属丰度均较低(29.2%比25.7%、16.8%比6.6%、8.8%比4.1%、10.0%比2.7%)，差异均有统计学意义(n Z＝-4.846、-4.192、-2.831、-1.993、-5.362、-3.405、-4.225，n P均<0.05)。与NAFLD组相比，二甲双胍治疗显著增加了普氏菌属、未分类的瘤胃球菌科、未分类的紫单胞菌科、未分类的毛螺菌科、梭状芽孢杆菌属ⅪⅤb的相对丰度，降低了罗姆布茨菌属、气球菌属、脱硫弧菌属的相对丰度。n 结论:二甲双胍可明显改善NAFLD大鼠的肠道菌群结构，抑制NAFLD的发生、发展。“,”Objective:To explore the effects of metformin on the intestinal microbiota of rats with non-alcoholic fatty liver disease (NAFLD).Methods:After two weeks of adaptive feeding, 24 male Sprague Dawley rats were divided into health control group, NAFLD group and metformin treatment group. NAFLD rat model was induced by high-fat diet. The blood samples were collected and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC) and triglyceride (TG) of each group were detected. The pathological changes of liver tissues were detected by hematoxylin-eosin (H-E) staining and oil red O staining. The α diversity analysis, including Chao index and Shannon index, and principal co-ordinates analysis (PCoA) were performed to study the structure of intestinal microbiota of rats according to the clustering information of operational taxonomic unit. n T test, one-way analysis of variance and rank sum test were used for statistical analysis.n Results:The levels of ALT, AST, TC and TG of the metformin treatment group were all lower than those of the NAFLD group ((58.43±4.89) U/L vs. (80.14±4.18) U/L, (160.14±13.04) U/L vs. (203.29±15.11) U/L, (1.534±0.113) mmol/L vs. (2.003±0.180) mmol/L, (0.724±0.105) mmol/L vs. (1.030±0.149) mmol/L, respectively), and the differences were statistically significant (n t=-8.926, -5.719, -5.828 and -4.446, all n P<0.05). The results of H-E staining and oil red O staining showed that after metformin treament, the liver cells of rats were arranged more orderly, the degree of swelling of hepatocytes was reduced, and the number of fat vacuoles decreased, the red staining of hepatocytes was significantly reduced, the number of lipid droplets reduced and lipid droplets were small in size and distributed unevenly in hepatocytes. The Chao and Shannon indexes of the metformin treatment group were both significantly lower than those of the NAFLD group (690(668, 703) vs. 722(683, 743) and 4.16(4.09, 4.42) vs. 4.40(4.20, 4.53)), and the differences were statistical significant (n Z=-2.106 and -2.083, both n P<0.05). The results of PCoA showed that the overall community bacteria composition was different between the NAFLD group and the metformin treatment group. At the phylum level, the abundance ofn Firmicutes, Proteobacteria and n Actinobacteria of gut microbiota of the NAFLD group was higher than those of the health control group (54.7% vs. 45.5%, 3.5% vs. 2.1%, 0.2% vs. 0.1%), and the abundance of n Bacteroidetes and n Tenericutes was lower than those of the health control group (41.3% vs. 51.9%, 9.4×10n -7 vs. 2.7×10n -3), and the differences were all statistically significant (n Z=-2.866, -2.726, -2.351, -2.901 and -4.881, all n P<0.05). At the genus level, compared with those of the health control group, the abundance ofn Blautia, Bacteroides and n Roseburia increased in the NAFLD group (0.6% vs. 11.8%, 0.9% vs. 6.5%, 1.1% vs. 7.1%), while the abundance of n Prevotella, Porphyromonadaceae_n unclassified, Ruminoccoccaceae_n unclassified and Lactobacillus decreased (29.2% vs. 25.7%, 16.8% vs. 6.6%, 8.8% vs. 4.1%, 10.0% vs. 2.7%), and the differences were all statistically significant (n Z=-4.846, -4.192, -2.831, -1.993, -5.362, -3.405 and -4.225, all n P<0.05). Compared with those of NAFLD group, the abundance ofn Prevotella, Porphyromonadaceae_n unclassified, Lachnospiraceae_n unclassified, Ruminoccoccaceae_n unclassified, and n Clostridium_ⅪⅤb increased in metformin treatment group, while the abundance of n Desulfovibrio, Aerococcus and n Romboustia decreased.n Conclusion:Metformin can not only improve the structure of intestinal microbiota in rats, but also inhibit the occurrence and development of NAFLD.