肠道菌群在非酒精性脂肪性肝病大鼠中的变化及意义

Changes of intestinal flora in rats with non-alcoholic fatty liver disease and its significance

目的分析非酒精性脂肪性肝病大鼠与正常大鼠的肠道菌群特征,探讨肠道菌群与非酒精性脂肪肝的关系。方法 20只雄性SD大鼠随机分为正常组(10只)、模型组(10只),分别饲以普通饲料、高脂饲料,12周后收集血、肝脏及盲肠黏膜等标本,检测血脂、肝功能指标,行HE染色明确肝组织病变程度,提取盲肠黏膜组织DNA行16S rDNA高通量Illumina测序检测肠道微生态变化。结果模型组血清丙氨酸氨基转移酶(ALT)、总胆固醇(TC)、LDL-C浓度比正常组明显升高(P<0.05),肠道菌群多样性分析显示正常组的sobs、chao、ace、shannon多样性指数均明显高于模型组(P<0.05),在菌门水平上,与正常组相比,模型组厚壁菌门/拟杆菌门的比值下降(2.192±0.144 vs 1.543±0.250,P=0.034),而疣微菌门的比例显著增加(0.088±0.016 vs 0.254±0.056,P=0.003);在菌属水平上,模型组乳杆菌属比正常组明显下降(0.683±0.207 vs 2.908±0.841,P=0.025)。结论肠道菌群变化在非酒精性脂肪性肝病的发病中发挥重要作用。

Objective To investigate the characteristics of intestinal flora in rats with non - alcoholic fatty liver disease, as well as the association between the intestinal flora and non - alcoholic fatty liver disease. Methods 20 male SD rats were randomly divided into the normal control group A（ 10 mice） fed with normal diet and NAFLD model group B （10 mice） fed with high -fat diet. After 12 weeks, blood, liver tissue and cecum mucosa specimens were collected. Blood lipid profile and liver function were detected. HE staining of the liver tissue was performed to identify pathological changes. DNA in the mucosal tissue and was extracted and sequenced using 16s rDNA high -throughput lllumina sequen- cing to detect the changes in intestinal flora. Results Serum ALT, TC and D - LDL concentrations in Group B were sig- nificantly higher than in Group A （ P 〈 0. 01 ）. Diversity indices including sobs, ehao, ace and shannon of intestinal flora in Group B significantly lower than in Group A （ P 〈 0. 05 ）. Compared with Group A, the ratio of Firmicutes to Bacte- roidetes in Group B significantly decreased（2. 192±0. 144 vs 1. 543±0. 250, P = 0. 034）, while proportion of Verru- comicrobia increased significantly （ 0. 088±0. 016 vs 0. 254±0. 056, P = 0. 003 ）. In the genus level, Lactobacillus in Group B significantly decreased than in Group A（0. 683±0. 207 vs 2. 908±0. 841, P =0. 025）. Conclusion There is a significant correlation between the changes of intestinal flora and the pathogenesis of NAFLD.