黄连素灌胃对非酒精性脂肪性肝炎小鼠肠道菌群的影响  

Modulation of gut microbiota with berberine improves nonalcoholic steatohepatitis in mice

作　　者：曹毅[1] 徐雷鸣[1] 潘勤[1] 王晓颖[2] 沈峰[1] 陈光瑜[1] 范建高[1] 

机构地区：[1]上海交通大学医学院附属新华医院消化内科,上海市200092 [2]上海交通大学医学院附属新华医院病理科,上海市200092

出　　处：《实用肝脏病杂志》2013年第2期137-140,共4页Journal of Practical Hepatology

基　　金：国家自然科学基金面上项目(编号:81070322);国家科技部973项目课题(编号:2012CB517501);上海市科委重点科技攻关项目(编号:10411956300;09140903500)

摘　　要：目的了解黄连素调节肠道菌群对非酒精性脂肪性肝炎的影响。方法将Babl/c小鼠随机分为对照组(n=10)、模型组(n=10)和干预组(n=15)。采用高脂饮食法制备脂肪肝模型,自第5周起,给予干预组小鼠黄连素(200mg·kg-1)灌胃至第13周结束。采用荧光定量PCR法相对定量检测CD14、IL-6、IL-1、TNF-α及进行盲肠内容物中双歧杆菌和乳酸菌计数。结果在13周末,模型组小鼠肝组织病理学检查显示明显的脂肪变和炎症改变,NAFLD活动度计分(NAS)为4.60±1.07,明显高于对照组(0.44±0.53,P<0.01);模型组血清ALT为346.00±142.01U/L,显著高于对照组(120.00±10.22U/L,P<0.01);肝组织IL-1mRNA为1.539±0.437、IL-6为0.580±0.083和TNF-α为4.482±0.820,显著高于对照组(分别为0.421±0.083、0.258±0.084和1.336±0.156,P均<0.01);模型组盲肠内容物中双歧杆菌数量为0.495±0.082,乳酸菌数量为0.010±0.006,显著低于对照组(分别为1.334±0.709和94.682±64.089,P均<0.05);与模型组比,干预组肝组织小叶内炎症明显减轻,NAS为2.73±0.90,显著低于模型组(4.60±1.07,P<0.01),生化指标较模型组改善,其中ALT为175.00±20.14U/L,显著低于模型组(346.00±142.01U/L,P<0.01),肝组织CD14为0.045±0.006、IL-1为0.243±0.067、IL-6为0.249±0.046和TNF-α为0.553±0.553,显著低于模型组(分别为0.321±0.106、1.539±0.437、0.580±0.083和4.482±0.820,P均<0.01),盲肠内容物中乳酸菌和双歧杆菌数量均较模型组增多,其中双歧杆菌(2.160±0.629)显著高于模型组(0.495±0.082,P<0.01)。结论高脂饮食喂养的Babl/c小鼠灌胃黄连素后,可能因为调整了肠道菌群,使肝内脂肪性炎症明显减轻。Objective To assess whether the gut microbiota is involved in the pathophysiology of nonalco- holic steatohepatitis （NASH）. Methods Babl/c mice were randomly divided into control（n=10）,model（n=10）and the therapeutic group （n=15）. The mice in control group were fed with normal diet and in other two groups were fed with high-fat diet. Meanwhile,the therapeutic group were treated with berberine （200mg.kg-1）since fifth week. The mice were sacrificed at the end of thirteen week. We assessed changes in bifidobacteria and lactobacillus in fecal contents and hepatic CD14, IL-I,IL-6 and TNF-α mRNA were detected by PCR. Results At the end of thirteenth week, the degree of steatosis and inflammation were more serious in the model group with the NAFLD activity score of 4.60±1.07,much higher than in the control （0.44±0.53,P〈0.01）;serum ALT in model group was obviously increased as compared with that in control group （346.00±142.01U/L vs. 120.00± 10.22U/L, P〈0.01 ） ; the hepatic levels of IL-1,IL-6 and TNF-α mRNA in therapeutic group were downregulated as compared with in mod- el group[0.243±0.067 vs. 1.539±0.437（P〈0.01）,0.249±0.046 vs. 0.580±0.083（P〈0.01）,and 0.553±0.553 vs. 4.482±0. 820 （P〈0.01）];the bifidobacteria and lactobacillus counts in fecal contents in berberine-treated group significantly improved as compared with in model group, especially for bifidobacteria （2.160±0.629 vs. 0.495±0.082,P〈0.01）. Conclusions The finding in our study demonstrates that berberine could modulate the microbiota in gut, which is conceivable that the stratezies for changing eut microbiota would improve NASH.

关 键 词：非酒精性脂肪性肝炎 肠道菌群 黄连素 Babl C小鼠 

分 类 号：R259[医药卫生—中西医结合]