生、制何首乌水提物改善MCD饲料诱导小鼠非酒精性脂肪性肝炎的研究  

Study on improvement provided by water extracts of Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata on non-alcoholic steatohepatitis in mice induced by MCD

作　　者：胡菲菲 郝占霞 张少波 盛雨辰[2] 季莉莉[1] HU Fei-fei;HAO Zhan-xia;ZHANG Shao-bo;SHENG Yu-chen;JI Li-li(the MOE Key Laboratory for Standardization of Chinese Medicines,the SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines,Shanghai Key Laboratory of Compound Chinese Medicines,Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Center for Drug Safety Evaluation and Research,Innovation Research Institute of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China)

机构地区：[1]上海中医药大学中药研究所中药标准化教育部重点实验室中药新资源与质量标准综合评价国家中医药管理局重点研究室上海市复方中药重点实验室,上海201203 [2]上海中医药大学创新中药研究院药物安全评价研究中心,上海201203

出　　处：《中国中药杂志》2020年第19期4732-4739,共8页China Journal of Chinese Materia Medica

基　　金：国家重点研发计划“中医药现代化研究”重点专项(2018YFC1707302);上海市进一步加快中医药事业发展三年行动计划项目[ZY(2018-2020)-CCCX-5002]。

摘　　要：该研究观察生何首乌和制何首乌水提物对非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)的改善作用及其初步机制。采用蛋氨酸胆碱缺乏饲料(methionine-choline-deficient diet,MCD)喂养小鼠6周进行造模,开始造模2周后小鼠灌胃50,100,200 mg·kg^-1的生何首乌水提物(Polygoni Multiflori Radix water extract,PMRWE)或制何首乌水提物(Polygoni Multiflori Radix Praeparata water extract,PMRPWE),连续给药4周。6周后结束实验,过程中持续监测小鼠体质量变化并记录;检测血清生化指标谷丙转氨酶(alanine aminotransferase,ALT)与谷草转氨酶(aspartate aminotransferase,AST)的活力;进行肝脏病理切片染色观察以及NAFLD活动性评分(NAFLD activity score,NAS)的计算;检测肝组织中活性氧(reactive oxygen species,ROS)水平,甘油三酯(triglyceride,TG)和游离脂肪酸(non-esterified fatty acids,NEFA)的含量,并进行肝组织油红O染色观察;应用荧光实时定量聚合酶链反应(quantitative polymerase chain reaction,qPCR)法检测肝组织中β氧化相关分子mRNA的表达。结果显示,100,200 mg·kg^-1的PMRWE及50,100,200 mg·kg^-1的PMRPWE能够改善MCD诱导NASH病变中的肝损伤;100,200 mg·kg^-1的PMRWE及50,100,200 mg·kg^-1的PMRPWE能够减少MCD诱导NASH病变中肝脏的脂质堆积;不同剂量的PMRPWE均能够逆转MCD诱导NASH病变中肝组织中下降的β氧化相关分子mRNA的水平。以上研究表明,PMRPWE与PMRWE能够通过促进肝脏脂肪酸β氧化,减少肝脏脂质累积,减轻肝脏损伤,从而发挥改善NASH的作用,且PMRPWE的作用明显优于PMRWE。This study aims to observe the improvement of non-alcoholic steatohepatitis(NASH)after using water extracts of Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata and explore their preliminary mechanism.Mice were fed with methionine-choline-deficent diet(MCD)for 6 weeks for modeling,and mice were orally given with 50,100,200 mg·kg^-1 of Polygoni Multiflori Radix water extract(PMRWE)or Polygoni Multiflori Radix Praeparata water extract(PMRPWE)at the last 4 weeks.During the whole experimental procedure,the body weight changes of the mice were monitored and recorded.Serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activities were detected;liver histopathological evaluation and NAFLD activity score(NAS)calculation were conducted,and the levels of reactive oxygen species(ROS)in liver tissues were analyzed.The contents of triglyceride(TG)and non-esterified fatty acids(NEFA)in liver tissues were detected,and oil red O staining of the liver tissues was conducted and observed.Quantitative polymerase chain reaction(qPCR)was used to detect hepatic mRNA expression ofβ-oxidation-related genes in mice.The results showed that PMRWE(100,200 mg·kg^-1)and PMRPWE(50,100,200 mg·kg^-1)alleviated liver damage in MCD-induced NASH in mice.PMRWE(100,200 mg·kg^-1)and PMRPWE(50,100,200 mg·kg^-1)reduced hepatic li-pid accumulation in mice with NASH.Different doses of PMRPWE inversed the decreased hepatic mRNA expression ofβ-oxidation-related genes in mice with NASH.This study indicated that PMRPWE and PMRWE could ameliorate MCD-induced NASH in mice by promoting fatty acidβoxidation,reducing liver lipid accumulation,and alleviating liver damage.Moreover,the protective effect of PMRPWE against MCD-induced NASH was better than PMRWE.

关 键 词：生何首乌水提物 制何首乌水提物 非酒精性脂肪性肝炎 β氧化 

分 类 号：R285.5[医药卫生—中药学]