肠道微生态对非酒精性脂肪性肝病发病与治疗的影响  

Influence of gut microecology on the pathogenesis and treatment of nonalcohofic fatty liver disease

作　　者：袁瑜[1] 孙之梅[1] 张扬[1] 梁芬芬[1] 何兴祥[1] 

机构地区：[1]广东药学院附属第一医院消化内科,广州510080

出　　处：《中华肝脏病杂志》2016年第5期375-379,共5页Chinese Journal of Hepatology

基　　金：广东省医学科研基金资助项目（A2014363）

摘　　要：目的高脂饮食诱导大鼠建立非酒精胜脂肪性肝病模型，动态观察建模过程及建模后改变肠道菌群对大鼠非酒精性脂肪性肝病形成及发展的影响。方法以高脂饮食诱导SD大鼠建立非酒精性脂肪性肝病模型，随机分为高脂组、抗生素预处理组、抗生素后处理组、限制饮食组及对照组，分别于不同喂养时段处死大鼠，应用16sRNA荧光定量PCR分析各组大鼠回盲部菌群变化，对各肝脏组织进行相应病理评分，酶比法检测血清及肝脏匀浆血脂水平。各组数据间比较采用样本均数f检验分析。结果与高脂组比较，各干预组中限制饮食组大鼠生存质量及生物化学指标改善最为显著。限制饮食组回肠末端益生菌（双歧杆菌、乳酸杆菌）数量逐渐回升，且随干预时间延长呈增加趋势，第10周差异最为显著，与高脂组分别比较（0．91±0．23对比0．28±0．12、0．28±0．12对比0．21±0．03），P值均〈0．05，差异均有统计学意义；而肠球菌数量则逐渐减少。各组肠杆菌变化比较，差异无统计学意义（P值均〉0．05）。在第10周，对照组、抗生素后处理组及限制饮食组肝脏病理评分分别为1．13±1．74、4．86±0．86、2．94±1．91均较高脂饮食组的7．09±2．03明显减低，P值均〉0．05，差异均有统计学意义。结论饮食结构改变及抗生素干预等手段均可通过调整肠道微生态缓解非酒精性脂肪性肝病的肝脏病变，继而从微生态角度为非酒精性脂肪性肝病防治提供新策略。Objective To establish a rat model of nonalcoholic fatty liver disease （NAFLD） using high-fat diet, and to dynamically observe the influence of the changes in gut microbiota on the development and progression of NAFLD in rats during and after modeling. Methods Sprague-Dawley rats were given high-fat diet to establish the model of NAFLD, and these rats were randomly divided into high-fat group, antibiotic pretreatment group, antibiotic treatment group, restricted diet group, and control group. The rats were sacrificed in different feeding periods, and 16sRNA fluorescent quantitative PCR was used to analyze the changes in ileocecal microbiota in rats. The liver pathological scores were determined, and enzymatic colorimetry was used to measure blood lipid level in serum and liver homogenate. The sample mean t-test was used for comparison between groups. Results Compared with the high-fat group, the restricted diet group showed the most significant improvements in quality of life and biochemical parameters. In the restricted diet group, the number of probiotics （Bifidobacterium and Lactobacillus） at the end of the ileum gradually increased and tended to increase over the time of intervention, and the most significant difference between this group and the high-fat group occurred at the 10th week （Bifidobacterium： 0.91±0.23 vs 0.28±0.12, P 〈 0.05; Lactobacillus： 0.78±0.04 vs 0.21±0,03, P 〈 0.05）, while the number of enterococci decreased. There were no significant differences in enteric bacilli between groups （all P 〉 0.05）. At the 10th week, the liver pathological scores in the control group, antibiotic treatment group, and restricted diet group were 1.13±1.74, 4.86±0.86, and 2.94±1.91, respectively, significantly lower than 7.09±2.03 in the high fat group （all P 〈 0.05）. Conclusion Diet structure change and antibiotic intervention can adjust gut microecology, alleviate the lesions of NAFLD, and thus provide new strategies for the prevention and treatment of NAFLD from the persp

关 键 词：治疗 肠道微生态 非酒精性脂肪性肝病 肝-肠轴 

分 类 号：R575[医药卫生—消化系统]