研究报告

植物发酵液对小鼠慢性酒精性肝损伤的保护作用

  • 刘春花 ,
  • 张逸凡 ,
  • 王蒲 ,
  • 李翔 ,
  • 梁岩
展开
  • 1(电子科技大学 资源与环境学院,四川 成都,611731)
    2(中国科学院深圳先进技术研究院,广东 深圳,518055)
    3(中国农业大学 食品科学与营养工程学院,北京,100083)
硕士, 助理研究员(梁岩教授为通讯作者,E-mail:yliang@uestc.edu.cn)

收稿日期: 2020-12-16

  修回日期: 2021-02-22

  网络出版日期: 2021-11-18

基金资助

国家自然科学基金(42077395);深圳市科技计划项目(JCYJ2017081816440501;YCYJ20180507182525623)

Protective effects of plant fermentation extracts on alcohol liver injury in mice

  • LIU Chunhua ,
  • ZHANG Yifan ,
  • WANG Pu ,
  • LI Xiang ,
  • LIANG Yan
Expand
  • 1(School of Resources and Environment, University of Electronic Science and Technology of China, Chengdu 611731, China)
    2(Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China)
    3(College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China)

Received date: 2020-12-16

  Revised date: 2021-02-22

  Online published: 2021-11-18

摘要

研究植物发酵液对慢性酒精性诱导小鼠肝损伤的保护作用及其机制。将雄性C57BL/6小鼠随机分为正常对照组、模型组、植物发酵液低、高剂量干预组[1.25和5.0 mL/kg体重(body weight,BW)]。每天正常对照组、模型组先灌胃无菌蒸馏水,植物发酵液干预组先灌胃相应剂量的植物发酵液,1 h后除正常对照组外各组小鼠均灌胃56°白酒(10 mL/kg BW)。实验结束后检测血清肝功能指标、细胞因子水平,肝脏乙醇代谢关键酶活力、抗氧化指标及有关基因mRNA表达水平等,并观察肝脏组织病理变化。结果表明,与慢性肝损伤模型组小鼠比较,干预8、10、12周后低高剂量植物发酵液均能够显著降低由慢性酒精摄入诱导的血清中天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)、丙氨酸氨基转移酶(alanine transaminase,ALT)活性的升高;苏木精-伊红染色结果显示,与模型组相比,植物发酵液高剂量组小鼠肝组织破坏程度减轻。植物发酵液能抑制肝脏中乙醇诱导的乙醇脱氢酶(alcohol dehydrogenase,ADH)、乙醛脱氢酶(aldehyde dehydrogenase,ALDH)活性升高及细胞色素P450家族成员2E1(recombinant cytochrome P450 2E1,Cyp2e1)mRNA表达下调,恢复机体乙醇代谢系统功能;提高肝组织中总超氧化物歧化酶(superoxide dismutase,SOD)、谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、总抗氧化能力(total antioxidant capacity,T-AOC)酶活力,抑制肝组织中脂质过氧化物丙二醛(malondialdehyde,MDA)含量的增加,提高肝脏抗氧化能力;上调血清细胞因子白细胞介素-1β(interleukin-1β,IL-1β)水平及肝脏白细胞介素-6(interleukin-6,Il6)mRNA的表达,下调肝脏信号转导与转录激活因子3(signal transducer and activator of transcription 3,Stat3)mRNA的表达,减轻炎症反应。可见,植物发酵液对慢性酒精诱导的小鼠肝损伤具有保护作用,可能与其恢复机体酒精代谢功能、减轻酒精代谢对机体造成的氧化损伤和炎症反应有关。

本文引用格式

刘春花 , 张逸凡 , 王蒲 , 李翔 , 梁岩 . 植物发酵液对小鼠慢性酒精性肝损伤的保护作用[J]. 食品与发酵工业, 2021 , 47(20) : 44 -51 . DOI: 10.13995/j.cnki.11-1802/ts.026454

Abstract

Protective effects of plant fermentation extracts (PFE) against alcohol-induced liver injury in mice was investigated. Male C57BL/6 mice were randomly divided into four groups. The normal control group and the model group were given distilled water per day, and the PFE low and high dose groups were given the corresponding PFE (1.25 or 5.00 mL/kg·BW). After 1 h, all groups were given 56 %vol liquor (10 mL/kg·BW) except the normal control group. The serum liver function indexes, cytokine levels, key enzyme activities of hepatic ethanol metabolism, antioxidant indexes and mRNA expression levels of related genes were detected, and the pathological changes of liver tissues were observed. PFE administration with ethanol resulted in prevention of ethanol-induced hepatotoxicity due to reductions of serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in mice treated with PFE for 8, 10,12 weeks. Results of hematoxylin-eosin staining showed that administration of PFE significantly alleviated alcohol-induced hepatocellular lesions in mice. Alcohol-induced upregulation of alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH) activity and downregulation of recombinant cytochrome P450 2E1 (Cyp2e1) mRNA expression in liver tissue were dramatically inhibited by PFE treatment. Mice treated with PFE showed increased hepatic antioxidant system with normal activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC), and reduced formation of malondialdehyde (MDA) in liver. Furthermore, PFE treatment also significantly inhibited the alcohol-induced inflammatory by increasing the hepatic interleukin-6 (Il6) mRNA expression and serum interleukin-1β (IL-1β) level, and the alcohol-induced increase of signal transducer and activator of transcription 3 (Stat3) mRNA expression. This study showed that PFE exerted hepatoprotective effects against alcohol-induced hepatic injury by mediating ethanol metabolism, oxidation and inflammation.

参考文献

[1] 王洪岩, 李鑫, 徐有青.酒精性肝病发病机制研究进展[J].实用肝脏病杂志, 2014(1):5-8.
WANG H Y, LI X, XU Y Q.Progress in the pathogenesis of alcoholic liver disease[J].Journal of Clinical Hepatology, 2014(1):5-8.
[2] FAN J G.Epidemiology of alcoholic and nonalcoholic fatty liver disease in China[J].Journal of Gastroenterology and Hepatology, 2013, 28:11-17.
[3] LOUVET A, MATHURIN P.Alcoholic liver disease:Mechanisms of injury and targeted treatment[J].Nature Reviews Gastroenterology & Hepatology, 2015, 12(4):231-242.
[4] LIU Y G, WANG J, LI L Z, et al.Hepatoprotective effects of Antrodia cinnamomea:The modulation of oxidative stress signaling in a mouse model of alcohol-induced acute liver injury[J].Oxidative Medicine and Cellular Longevity, 2017.DOI:10.1155/2017/7841823.
[5] 刘岩, 苏琳.酒精性肝病基层诊疗指南(2019年)[J].临床肝胆病杂志, 2021, 37(1):36-40.
LIU Y, SU L.Guideline for primary care of alcoholic liver disease(2019)[J].Journal of Clinical Hepatology, 2021, 37(1):36-40.
[6] 饶智, 陈彦坤, 刘斌, 等.“药食同源”植物酵素研究进展[J].食品与发酵工业, 2020, 46(9):290-294.
RAO Z, CHEN Y K, LIU B, et al.Research progress on “herb-food homology’ plant Jiaosu[J].Food and Fermentation Industries, 2020, 46(9):290-294.
[7] 赵芳芳, 莫雅雯, 蒋增良, 等.功能性微生物酵素产品的研究进展[J].食品与发酵工业, 2016, 42(7):283-287.
ZHAO F F, MO Y W, JIANG Z L, et al.Research progress on functional microbial ferment product[J].Food and Fermentation Industries, 2016, 42(7):283-287.
[8] 陈宏运, 崔红燕, 吴彬彬, 等.植物发酵液对D-半乳糖致衰老模型小鼠的抗氧化活性研究[J].现代食品科技, 2015, 31(8):7-11;17.
CHEN H Y, CUI H Y, WU B B, et al.Antioxidant activity of fermented plant extracts(FPE) in a mouse model of D-galactose-induced aging[J].Modern Food Science and Technology, 2015, 31(8):7-11;17.
[9] 刘春花, 吴彬彬, 陈宏运, 等.植物发酵液(酵素)对小鼠免疫功能的影响[J].食品研究与开发, 2016, 37(18):173-178.
LIU C H, WU B B, CHEN H Y, et al.The immunomodulatory effect of the plant fermentation extracts(PFE) in mice[J].Food Research and Development, 2016, 37(18):173-178.
[10] 杨莉丽, 吴彬彬, 梁岩.植物发酵液对肠易激综合征患者肠道菌群的调节[J].世界华人消化杂志, 2016, 24(19):2 982-2 987.
YANG L L, WU B B, LIANG Y.Effects of plant fermentation extract on intestinal microbiota in patients with irritable bowel syndrome[J].World Chinese Journal of Digestology, 2016, 24(19):2 982-2 987.
[11] 汤超, 汤文凡, 黄玉琴, 等.木瓜发酵液对小鼠四氯化碳诱发肝损伤的防护作用[J].食品科学, 2013, 34(13):271-274.
TANG C, TANG W F, HUANG Y Q, et al.Protective effect of fermented Chaenomeles speciosa juice on acute hepatic injury induced in mice by carbon tetrachloride[J].Food Science, 2013, 34(13):271-274.
[12] 王雨珊, 游颖, 李万丛, 等.发酵乳杆菌发酵人参缓解酒精性脂肪肝损伤的研究[J].食品科技, 2018, 43(5):59-66.
WANG Y S, YOU Y, LI W C, et al.Alleviation of alcoholic liver injury by fermented ginseng with Lactobacillus fermentum[J].Food Science and Technology, 2018, 43(5):59-66.
[13] 秦松, 王君, 高志鹏, 等.奇魅植物酵素对小鼠酒精性肝损伤保护作用的研究[J].重庆医学, 2016, 45(10):1 323-1 325.
QIN S, WANG J, GAO Z P, et al.Protection of Qimei fermented beverage against alcohol-induced liver injury in mice[J].Chongqing Medicine, 2016, 45(10):1 323-1 325.
[14] 谷大为, 陈志敏, 周明, 等.果蔬发酵液对小鼠酒精性肝损伤的保护作用及氧化应激机制[J].营养学报, 2015, 37(4):366-371.
GU D W, CHEN Z M, ZHOU M, et al.The protective effect of vegetables and fruits fermentation liquid in mice with alcoholic liver damage and its antioxidative mechanism[J].Acta Nutrimenta Sinica, 2015, 37(4):366-371.
[15] 曲佳乐, 赵金凤, 皮子凤, 等.植物酵素解酒护肝保健功能研究[J].食品科技, 2013, 38(9):51-55.
QU J L, ZHAO J F, PI Z F, et al.The health care function for antialcoholism and liver protection of plant enzyme[J].Food Science and Technology, 2013, 38(9):51-55.
[16] 朱诗雅, 翟齐啸, 赵星, 等.不同乳杆菌缓解慢性酒精性肝损伤的作用比较[J].食品与发酵工业, 2019, 45(22):20-26.
ZHU S Y, ZHAI Q X, ZHAO X, et al.Comparison of the alleviation effects of different Lactobacilli on chronic alcohol-induced liver injury[J].Food and Fermentation Industries, 2019, 45(22):20-26.
[17] 牛佳卉, 袁静, 张慧芳, 等.王浆酸对小鼠酒精性肝损伤的保护作用[J].食品工业科技, 2020, 41(3):291-296.
NIU J H, YUAN J, ZHANG H F, et al.Protective effect of royal jelly acid on the alcohol liver injury in mice[J].Science and Technology of Food Industry, 2020, 41(3):291-296.
[18] DAI C, LI D, GONG L, et al.Curcumin ameliorates furazolidone-induced DNA damage and apoptosis in human hepatocyte L02 cells by inhibiting ROS production and mitochondrial pathway[J].Molecules, 2016, 21(8):1 061.
[19] YAMASHITA H, GOTO M, MATSUI-YUASA I, et al.Ecklonia cava polyphenol has a protective effect against ethanol-induced liver injury in a cyclic AMP-dependent manner[J].Marine Drugs, 2015, 13(6):3 877-3 891.
[20] 黄佩佩, 吕丽, 刘传新.细胞色素P4502E1及其基因多态性与酒精依赖的关系[J].四川精神卫生, 2020, 33(1):92-96.
HUANG P P, LYU L, LIU C X.Relationship between cytochrome P4502E1 and its gene polymorphism and alcohol dependence[J].Sichuan Mental Health, 2020, 33(1):92-96.
[21] LI C, LI L, YANG C F, et al.Hepatoprotective effects of methyl ferulic acid on alcohol-induced liver oxidative injury in mice by inhibiting the NOX4/ROS-MAPK pathway[J].Biochemical and Biophysical Research Communications, 2017, 493(1):277-285.
[22] HUANG Q H, XU L Q, LIU Y H, et al.Polydatin protects rat liver against ethanol-induced injury:Involvement of CYP2E1/ROS/Nrf2 and TLR4/NF-κB p65 pathway[J].Evidence-Based Complementary and Alternative Medicine, 2017.DOI:10.1155/2017/7953850.
[23] JELSKI W, SZMITKOWSKI M.Alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in the cancer diseases[J].Clinica Chimica Acta, 2008, 395(1-2):1-5.
[24] 齐冰. 肝癌患者肝脏中乙醇脱氢酶和乙醛脱氢酶活性变化[D].郑州:郑州大学, 2015.
QI B.Liver alcohol dehydrogenases and aldehyde dehydrogenases activity of liver cancer patients[D].Zhengzhou:Zhengzhou University, 2015.
[25] LAM P, CHEUNG F, TAN H Y, et al.Hepatoprotective effects of Chinese medicinal herbs:A focus on anti-inflammatory and anti-oxidative activities[J].International Journal of Molecular Sciences, 2016, 17(4):465.
[26] MANDREKAR P, SZABO G.Signalling pathways in alcohol-induced liver inflammation[J].Journal of Hepatology, 2009, 50(6):1 258-1 266.
[27] BIRD G L, SHERON N, GOKA A K, et al.Increased plasma tumor necrosis factor in severe alcoholic hepatitis[J].Annals of Internal Medicine, 1990, 112(12):917-920.
[28] AN L, WANG X D, CEDERBAUM A I.Cytokines in alcoholic liver disease[J].Archives of Toxicology, 2012, 86(9):1 337-1 348.
[29] 伍振辉, 孟娴, 胡佳伟, 等.TLR4-MyD88- NF-κB信号通路与肝炎-肝纤维化-肝癌轴相关性研究进展[J].国际药学研究杂志, 2017, 44(5):396-401.
WU Z H, MENG X, HU J W, et al.Research progress on the correlation between TLR4-MyD88-NF-κB signalling pathways and the hepatic inflammation-fibrosis-cancer axis[J].Journal of International Pharmaceutical Research, 2017, 44(5):396-401.
[30] 崔香丹, 金武丕, 孟繁平.Bcl-2和NF-κB在大鼠酒精性肝病中的表达及相关性[J].中国现代医学杂志, 2009, 19(1):55-58;63.
CUI X D, JIN W P, MENG F P.Expression of Bcl-2 and NF-κB in alcoholic liver disease in rats and their dependability[J].China Journal of Modern Medicine, 2009, 19(1):55-58;63.
[31] NUNES K, FLORENTINO R M, FRANCA A, et al.Polymorphism in the promoter region of NFE2L2 gene is a genetic marker of susceptibility to cirrhosis associated with alcohol abuse[J].International Journal of Molecular Sciences, 2019, 20(14):3 589.
[32] SUN J, FU J Q, ZHONG Y, et al.NRF2 mitigates acute alcohol-induced hepatic and pancreatic injury in mice[J].Food and Chemical Toxicology, 2018, 121:495-503.
[33] 李永丽. STAT3, 自噬在非酒精性脂肪性肝炎炎症中的作用及二甲双胍抗炎机制的研究[D].石家庄:河北医科大学, 2019.
LI Y L.The role of STAT3 and autophagy of the inflammation of non-alcoholic steatohepatitis and the anti-inflammatory mechanism of metformin[D].Shijiazhuang:Hebei Medical University, 2019.
[34] BELLONI L, DI COCCO S, GUERRIERI F, et al.Targeting a phospho-STAT3-miRNAs pathway improves vesicular hepatic steatosis in an in vitro and in vivo model[J].Scientific Reports, 2018, 8(1):13638.
文章导航

/