

浏览全部资源
扫码关注微信
安徽中医药大学 中西医结合学院,第一附属医院,合肥 230012
Received:28 August 2021,
Published Online:19 October 2021,
Published:05 December 2021
移动端阅览
汪丹丹,陈文静,贾步云等.非酒精性脂肪性肝病动物模型研究进展[J].中国实验方剂学杂志,2021,27(23):245-250.
WANG Dan-dan,CHEN Wen-jing,JIA Bu-yun,et al.Animal Models of Nonalcoholic Fatty Liver Disease:A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(23):245-250.
汪丹丹,陈文静,贾步云等.非酒精性脂肪性肝病动物模型研究进展[J].中国实验方剂学杂志,2021,27(23):245-250. DOI: 10.13422/j.cnki.syfjx.20212337.
WANG Dan-dan,CHEN Wen-jing,JIA Bu-yun,et al.Animal Models of Nonalcoholic Fatty Liver Disease:A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(23):245-250. DOI: 10.13422/j.cnki.syfjx.20212337.
非酒精性脂肪性肝病(NAFLD)是一种以肝细胞内脂质过度蓄积,与胰岛素抵抗和遗传易感密切相关的代谢应激性肝损伤。中医称其为“肝癖”。NAFLD影响着全球约25%的人,是世界卫生保健系统的主要负担,但其确切发病机制尚不清楚,开展NAFLD相关的基础研究具有重要的临床意义和社会价值。动物模型作为研究NAFLD的重要工具,对于明确NAFLD发生、发展的病理生理学机制尤为重要,近年来国内外关于NAFLD的造模方法不断更新,尤其是中医证候方面的模型取得了一定的发展。笔者通过查阅和整理近年来国内外的相关文献资料,对NAFLD动物模型复制方法进行了总结。该文对膳食诱导(高脂饲料、高脂高果糖饲料、高脂高胆固醇饲料、蛋氨酸胆碱缺乏饲料)模型、遗传基因缺陷[瘦素基因缺乏(Lep
ob
/Lep
ob
)]小鼠、常染色体隐性糖尿病基因纯合子缺乏(ob/ob)小鼠、携带突变Alms1基因(foz/foz)小鼠,FATZO小鼠)+特殊饮食模型、中医证候(肝郁脾虚证、痰湿证、血瘀证、痰瘀互结证、气滞血瘀证)模型进行综述,并对其优缺点进行探讨,以期为制备更科学合理、经济便捷的NAFLD动物模型提供参考,为深入研究NAFLD的发病机制、预防与治疗NAFLD奠定基础。
Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress-induced liver injury characterized by excessive lipid accumulation in hepatocytes, which is closely related to insulin resistance and genetic susceptibility. It falls into the category of "liver lump" in traditional Chinese medicine (TCM). NAFLD affects about 25% of the population worldwide and has become a major burden of the world health care system. However, its exact pathogenesis remains unclear. Conducting the basic research on NAFLD is of great clinical significance and social value. As an important tool for NAFLD research, animal model plays a particularly important role in clarifying the pathophysiological mechanism of NAFLD. In recent years, the modeling methods for NAFLD in China and abroad have been constantly updated, and in particular, certain progress has been made in the duplication of TCM syndrome models. By consulting and sorting out the relevant literature published in recent years in China and abroad, the author summarized the replication methods of NAFLD animal models. This paper reviewed the advantages and disadvantages of models established via dietary induction (high-fat feed, high-fat and high-fructose feed, high-fat and high-cholesterol feed, and methionine choline-deficient feed), models with genetic defects [leptin-deficiency (Lep
ob
/Lep
ob
), autosomal recessive diabetes gene homozygous deficiency (ob/ob), Alms1 gene (foz/foz) mutation, and FATZO mice] and exposure to special diets, and models for TCM syndromes (liver depression and spleen deficiency syndrome, phlegm-dampness syndrome, blood stasis syndrome, combined phlegm and stasis syndrome, and qi stagnation and blood stasis syndrome), in order to provide reference for the preparation of more scientific, reasonable, economical, and convenient animal models of NAFLD, thus laying a foundation for in-depth study of the pathogenesis, prevention, and treatment of NAFLD.
中华医学会肝病学分会脂肪肝和酒精性肝病学组 , 中国医师协会脂肪性肝病专家委员会 . 非酒精性脂肪性肝病防治指南(2018年更新版) [J]. 实用肝脏病杂志 , 2018 , 21 ( 2 ): 177 - 186 .
VAN H , VONGHIA L , FRANCQUE S . Animal models of nonalcoholic fatty liver disease-a starter's guide [J]. Nutrients , 2017 , 9 ( 10 ): 1072 .
张译之 , 张晓慧 , 陈煜 . 非酒精性脂肪性肝病动物模型研究进展 [J]. 实用肝脏病杂志 , 2021 , 24 ( 5 ): 761 - 764 .
SAAD Z A , KHODDER D M , ZAITONE S A , et al . Exenatide ameliorates experimental non-alcoholic fatty liver in rats via suppression of toll-like receptor4/NF- κ B signaling:comparison to metformin [J]. Life Sci , 2020 , 253 : 117725 .
IBRAHIM S H , HIRSOVA P , MALHI H , et al . Animal models of nonalcoholic steatohepatitis:eat,delete,and inflame [J]. Dig Dis Sci , 2016 , 61 ( 5 ): 1325 - 1336 .
WANG W , ZHAO J , GUI W , et al . Tauroursodeoxycholic acid inhibits intestinal inflammation and barrier disruption in mice with non-alcoholic fatty liver disease [J]. Br J Pharmacol , 2018 , 175 ( 3 ): 469 - 484 .
JIANG M , WU N , CHEN X , et al . Pathogenesis of and major animal models used for nonalcoholic fatty liver disease [J]. J Int Med Res , 2019 , 47 ( 4 ): 1453 - 1466 .
SUBRAMANIAN S , GOODSPEED L , WANG S , et al . Dietary cholesterol exacerbates hepatic steatosis and inflammation in obese LDL receptor-deficient mice [J]. J Lipid Res , 2011 , 52 : 1626 - 1635 .
ABDELMALEK M F , SUZUKI A , GUY C , et al . Increased fructose consumption is associated with fibrosis severity in patients with non-alcoholic fatty liver disease [J]. Hepatology , 2010 , 51 : 1961 - 1971 .
SAVARD C , TARTAGLIONE E V , KUVER R , et al . Synergistic interaction of dietary cholesterol and dietary fat in inducing experimental steatohepatitis [J]. Hepatology , 2013 , 57 : 81 - 92 .
LAU J K , ZHANG X , YU J . Animal models of non-alcoholic fatty liver disease:current perspectives and recent advances [J]. J Pathol , 2017 , 241 ( 1 ): 36 - 44 .
ITAGAKI H , SHIMIZU K , MORIKAWA S , et al . Morphological and functional characterization of nonalcoholic fatty liver disease induced by a methionine-choline-deficient diet in C57BL/6 mice [J]. Int J Clin Exp Pathol , 2013 , 6 ( 12 ): 2683 - 2696 .
VESKOVIC M , LABUDOVIC-BOROVIC M , MLADENOVIC D , et al . Effect of betaine supplementation on liver tissue and ultrastructural changes in methionine-choline-deficient diet-induced NAFLD [J]. Microsc Microanal , 2020 , 26 ( 5 ): 997 - 1006 .
SAMANO HERNANDEZ L , FOERRO R , MARCHAL A , et al . Beneficial and deleterious effects of sitagliptin on a methionine/choline-deficient diet-induced steatohepatitis in rats [J]. Biochimie , 2021 , 181 : 240 - 248 .
PIERANTONELLI I , SVEGLIATI-BARONI G . Nonalcoholic fatty liver disease:basic pathogenetic mechanisms in the progression from NAFLD to NASH [J]. Transplantation , 2019 , 103 ( 1 ): e1 - e13 .
SANCHES S C , RAMALHO L N , AUGUSTO M J , et al . Nonalcoholic steatohepatitis:a search for factual animal models [J]. Biomed Res Int , 2015 , 2015 : 574832 .
MOLLAH M L , YANG H S , JEON S , et al . Overaccumulation of fat caused rapid reproductive senescence but not loss of ovarian reserve in ob/ob Mice [J]. J Endocr Soc , 2020 , 5 ( 1 ): 168 .
KRISTIANSEN M N , VEIDAL S S , RIGBOIT K T , et al . Obese diet-induced mouse models of nonalcoholic steatohepatitis-tracking disease by liver biopsy [J]. World J Hepatol , 2016 , 8 : 673 - 684 .
YANG H , YANG T , HENG C , et al . Quercetin improves nonalcoholic fatty liver by ameliorating inflammation,oxidative stress,and lipid metabolism in db/db mice [J]. Phytother Res , 2019 , 33 ( 12 ): 3140 - 3152 .
POEKES L , GILLARD J , FARRELL G C , et al . Activation of brown adipose tissue enhances the efficacy of caloric restriction for treatment of nonalcoholic steatohepatitis [J]. Lab Invest , 2019 , 99 ( 1 ): 4 - 16 .
FARRELL G C , MRIDHA A R , YEH M M , et al . Strain dependence of diet-induced NASH and liver fibrosis in obese mice is linked to diabetes and inflammatory phenotype [J]. Liver Int , 2014 , 34 : 1084 - 1093 .
DROZ B A , SNEED B L , JACKSON C V , et al . Correlation of disease severity with body weight and high fat diet in the FATZO/Pco mouse [J]. PLoS One , 2017 , 12 ( 6 ): e0179808 .
POMPILI S , VETUSCHI A , GAUDIO E , et al . Long-term abuse of a high-carbohydrate diet is as harmful as a high-fat diet for development and progression of liver injury in a mouse model of NAFLD/NASH [J]. Nutrition , 2020 , 75-76 : 110782 .
KAMM D R , PYILES K D , SHARPE M C , et al . Novel insulin sensitizer MSDC-0602K improves insulinemia and fatty liver disease in mice,alone and in combination with liraglutide [J]. J Biol Chem , 2021 , 296 : 100807 .
刘杨 , 李明磊 , 贾飞 , 等 . 逍遥散对非酒精性脂肪性肝炎肝郁脾虚证大鼠TLR-4/TRIF信号转导通路的影响 [J]. 中国实验方剂学杂志 , 2018 , 24 ( 17 ): 108 - 113 .
贾飞 , 苗宇船 , 苏赵威 , 等 . 逍遥丸对肝郁脾虚证非酒精性脂肪肝病大鼠TLR4表达的影响 [J]. 山西中医 , 2016 , 32 ( 3 ): 48 - 50 .
刘涛 , 徐秋玲 , 杨叔禹 . 高脂饮食诱导痰湿证动物模型的建立与评价 [J]. 长春中医药大学学报 , 2009 , 25 ( 3 ): 333 - 335 .
陈芝芸 , 蔡丹莉 , 严茂祥 , 等 . 血瘀型非酒精性脂肪性肝病病证结合模型的建立和评价 [J]. 中华中医药杂志 , 2012 , 27 ( 3 ): 727 - 731 .
朱晓宁 , 汪静 , 郑丁 , 等 . 非酒精性脂肪性肝病痰瘀互结证大鼠模型的构建及评价 [J]. 中医杂志 , 2017 , 58 ( 22 ): 1953 - 1956 .
石贺 . 化瘀软肝胶囊对气滞血瘀型非酒精性脂肪性肝病大鼠糖脂代谢相关酶及氧化产物的影响 [D]. 兰州 : 甘肃中医药大学 , 2019 .
ENG J M , ESTALL J L . Diet-induced models of non-alcoholic fatty liver disease:food for thought on sugar,fat,and cholesterol [J]. Cells , 2021 , 10 ( 7 ): 1805 .
0
Views
18
下载量
2
CSCD
Publicity Resources
Related Articles
Related Author
Related Institution
京公网安备11010802024621