余甘子鞣质对代谢相关脂肪性肝病小鼠脂质代谢及肠道菌群的调节作用  

Effect and mechanism of tannin part of Phyllanthus emblica on lipid metabolism and intestinal flora in MAFLD mice

作　　者：张艳鹤[1] 郑亚云 芦超 常文娟[1] 靳菲菲[1] 李锦秀 张超 ZHANG Yanhe;ZHENG Yayun;LU Chao;CHANG Wenjuan;JIN Feifei;LI Jinxiu;ZHANG Chao(Department of Gastroenterology,Jiaozuo People's Hospital,Jiaozuo 454000,China;Pharmacology Laboratory,Henan Academy of Medical Sciences,Zhengzhou 450052,China)

机构地区：[1]焦作市人民医院中西医结合消化内科,河南焦作454000 [2]河南省医药科学研究院药理研究室,河南郑州450052

出　　处：《药物评价研究》2022年第2期287-293,共7页Drug Evaluation Research

基　　金：河南省科技发展计划(152300410160)。

摘　　要：目的研究余甘子Phyllanthus emblica L.鞣质对代谢相关脂肪性肝病(MAFLD)小鼠脂质代谢及肠道菌群的调节作用。方法将C57BL/6小鼠随机分为对照组、模型组和余甘子鞣质低、高剂量(200、400 mg·kg^(−1))组及非诺贝特(阳性药,50 mg·kg^(−1))组,每组10只。对照组小鼠常规饲料喂养,其余各组小鼠均给予高脂饲料喂养,建立MAFLD小鼠模型;ig给予相应药物干预,对照组及模型组给予同体积生理盐水,每天1次,连续给药8周。处死小鼠,收集血液、肝脏、粪便。计算肝脏系数;HE染色法观察肝组织病理学变化;试剂盒法检测小鼠血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、三酰甘油(TG)、总胆固醇(TC)含量;实时荧光定量PCR(qRT-PCR)及Western blotting法检测肝组织中固醇调节元件结合蛋白(SREBP-1)、脂肪酸合成酶(FASN)、乙酰辅酶A羧化酶(ACC)mRNA和蛋白表达量;PCR扩增法检测实验前后小鼠粪便双歧杆菌、乳酸杆菌的含量变化。结果与模型组比较,低、高剂量余甘子鞣质干预后小鼠肝脏系数显著降低(P<0.05、0.01),小鼠肝组织脂肪变程度减轻;小鼠血清中ALT、AST、TG、TC水平均显著降低(P<0.05、0.01);肝组织中SREBP-1、FASN、ACC mRNA和蛋白水平均显著降低(P<0.05、0.01);粪便中双歧杆菌、乳酸杆菌的含量显著升高(P<0.01)。结论余甘子鞣质能够通过SREBP-1/FASN/ACC通路调节脂质代谢、改善肠道菌群平衡,改善MAFLD。Objective To study the effect of tannin part of Phyllanthus emblica on fatty acid metabolism and intestinal flora in metabolic associated fatty liver disease(MAFLD)mice.Methods C57BL/6 mice were randomly divided into control group,model group,low and high dose(200 and 400 mg·kg^(−1))tannin part of Phyllanthus emblica group and fenofibrate(positive,50 mg·kg^(−1))group,10 rats in each group.Control mice fed normal diet,the other groups of mice were given a high fat diet to establish the MAFLD model.At the same time,tannin part of Phyllanthus emblica low and high dose drugs were given to the corresponding drug intervention,and the control group and model group were given the same volume saline.After eight weeks of continuous administration,mice were executed to collect blood,liver tissue and faeces samples.HE staining method was used to observe the pathological changes of liver tissue and the biochemical instrument was used to detect the content of ALT,AST,TG and TC in serum of mice.Western blotting and qRT-PCR were used to detect the expression of gene proteins such as SREBP-1,FASN and ACC in liver tissue,and qPCR to detect the number of Bifidobacterium and Lactobacillus in mouse faeces.Results Compared with model group,in low and high dose tannin part of Phyllanthus emblica group,the liver index in mice was significantly decreased(P<0.05,0.01),the degree of fat change in liver tissue was alleviated,the serum levels of ALT,AST,TG and TC were significantly decreased(P<0.05,0.01),mRNA and protein levels of SREBP-1,FASN andACC in liver tissue were significantly decreased(P<0.05,0.01),the contents of Bifidobacteria and Lactobacillus in feces were significantly increased(P<0.01).Conclusion The tannin part of Phyllanthus emblica can lipid metabolism through SREBP-1/FASN pathway,and can regulate intestinal flora balance,which has a certain preventive effect on MAFLD.

关 键 词：余甘子 鞣质 代谢相关脂肪性肝病 肠道菌群 固醇调节元件结合蛋白(SREBP-1) 脂肪酸合成酶(FASN) 乙酰辅酶A羧化酶(ACC) 

分 类 号：R285.5[医药卫生—中药学]