盐酸小檗碱对高脂饮食诱导的非酒精性脂肪性肝病大鼠肠道菌群的影响

Effects of berberine on gut microbiota of rats with non-alcoholic fatty liver disease induced by high-fat diet

目的观察盐酸小檗碱对高脂饮食诱导的非酒精性脂肪性肝病(NAFLD)大鼠肠道菌群的影响。方法 18只雄性SD大鼠随机分为普通饲料喂养组(正常对照组)、高脂饮食诱导NAFLD组(NAFLD组)和高脂饮食诱导NAFLD小檗碱干预组(小檗碱干预组),每组6只。采用16SrRNA序列分析法研究3组大鼠肠道菌群的变化;观察3组大鼠肝脏和回肠组织形态学改变。结果 3组大鼠的肠道菌群主要分布在拟杆菌门和厚壁菌门;与正常对照组比较,NAFLD组的厚壁菌门比例显著增高(P<0.05),拟杆菌门比例及有益菌乳酸菌属比例则显著降低(P<0.01);与NAFLD组比较,小檗碱干预组的厚壁菌门比例显著下降(P<0.01),拟杆菌门比例和有益菌乳酸菌属比例显著增高(P<0.01)。肝脏组织学检查发现:正常对照组大鼠肝脏细胞排列正常,未见脂肪滴和炎症细胞浸润;NAFLD组大鼠肝脏组织出现大量的脂肪变性,肝细胞排列较正常对照组紊乱;小檗碱干预组大鼠肝脏组织仍有脂肪变性,但脂肪变性程度较NAFLD组减轻。回肠组织学检查发现:正常对照组大鼠回肠绒毛排列整齐、紧凑,表面结构完整;NAFLD组大鼠回肠绒毛出现断裂、缺失,间隙增宽;小檗碱干预组大鼠回肠绒毛排列较为整齐,断裂、缺失较NAFLD组少。结论小檗碱可以改善高脂饮食所诱导的NAFLD,其机制可能与改变肠道菌群的结构及减轻高脂饮食导致的肠道黏膜损伤有关。

Objective To observe the effects of berberine on gut microbiota of rats with non-alcoholic fatty liver disease （NAFLD） induced by high-fat diet. Methods A total of 18 male SD rats were randomly divided into the normal diet group （ND group, n =6）, high-fat diet-induced NAFLD group （NAFLD group, n =6）, and high-fat diet-induced NAFLD intervened by berberine group （berberine intervention group, n =6）. Changes of gut microbiota were investigated by the 16SrRNA gene sequence analysis and morphological changes of liver and ileum tissue were observed. Results Gut microbiota were mainly Firmicutes and Bacteroidetes. Compared with the ND group, the ratio of Firmicutes of the NAFLD group was significantly higher （ P 〈 0.05）, while ratios of Bacteroidetes and beneficial bacteria Lactobacillus were significandy lower （P〈0.01）. Compared with the NAFLD group, the ratio of Firmicutes of the berberine intervention group was significant lower （P〈0. 01）, while ratios of Bacteroidetes and beneficial bacteria LactobadUus were significandy higher （P〈0.01）. Results of the liver histological examination of liver showed that the arrangement of hepatic cells of the ND group was normal and fatty infiltration and inflammatory cell infiltration were not observed. Compared with the ND group, the arrangement of hepatic cells of the NAFLD group was disordered and much steatosis was observed. Thesteatosis was observed in liver tissues of the berberine intervention group, but less serious than the NAFLD group. Results of the histological examination of ileum showed that the ileum mucosal villus of the ND group arranged neatly and tight and the surface structure was integrated. The ileum mucosal villus of the NAFLD group was broke or lost and the gap of intervillous space widened. The ileum mucosal villus of the berberine intervention group arranged relatively neatly and less ileum mucosal villus was broke or lost than that of the NAFLD group. Conclusion Berberine can relieve the non-alcoholic fatty liver disease induced by high fat diet. The mechanism may be relevant to the changes of structure of gut microbiota and the decrease of intestinal mucosa damages caused by high-fat diet.