肝纤维化动物实验模型的研究进展
南洋1 董辉1 王志刚1 刘树民2▲
1.黑龙江中医药大学药学院,黑龙江哈尔滨 150040;
2.黑龙江中医药大学中医药研究院,黑龙江哈尔滨 150040
Research progress of animal experimental model of hepatic fibrosis#br#
NAN Yang1 DONG Hui1 WANG Zhigang1 LIU Shumin2▲
1.College of Pharmacy, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China;
2.Chinese Medicine Research Institute, Heilongjiang University of Chinese Medicine, Heilongjiang Province, Harbin 150040, China
摘要 肝纤维化的致病因素在于创伤愈合反应的渐进过程,肝纤维化可进展为肝硬化,并进一步发展为肝癌。目前科研人员在肝纤维化研究方面付出了相当大的努力,希望通过阐明这种疾病的发病机制,建立有效的诊断和治疗方案。本文目的是从动物实验模型建立的理论基础、实验动物的选择、操作方法、试剂的用量、注意事项和模型的优缺点及适用方向进行详细分析,希望可以借此帮助科研人员根据不同的实验需求,在研究肝纤维化时做出更好的选择。肝纤维化的动物实验模型需要注意在建模时的随行观察,以免给药过度形成更为严重的疾病模型如肝硬化模型等。肝纤维化的动物实验方法较多,有化学方法、饮食法、手术法、感染法和遗传修饰小鼠模型,通过对文献内容的比较和分析,发现四氯化碳法是比较普遍适用的方法,具有方法简单、可靠性强、价格低廉等优点。
关键词 :
肝纤维化 ,
动物模型 ,
星状细胞 ,
四氯化碳
Abstract :The pathogenesis of hepatic fibrosis is the progressive process of wound healing reaction, hepatic fibrosis can progress to cirrhosis, and further development of liver cancer. At present, researchers have paid considerable efforts in the research of hepatic fibrosis, hoping to clarify the pathogenesis of this disease and establish effective diagnosis and treatment plan. The purpose of this article is from the animal experimental model of theoretical basis, the selection of experimental animal, the operation method, the usage of reagents, the matters needing attention, and the advantages and disadvantages of the model, and its application, hoping to help in accordance with the different requirements of the scientific research personnel and make better choices in the study of liver fibrosis. The animal experimental model of hepatic fibrosis needs to be observed during the modeling to avoid excessive administration of drugs to form a more serious disease model such as cirrhosis. There are many animal experimental methods for hepatic fibrosis, including chemical methods, dietary methods, surgical methods, infection methods, and genetically modified mouse models. Through comparison and analysis of literature contents, it is found that carbon tetrachloride method is generally applicable and has the advantages of simple method, high reliability, and low price.
Key words :
Hepatic fibrosis
Animal model
Stellate cell
Carbon tetrachloride
基金资助: 国家自然科学基金面上项目(81573592);
国家自然科学基金青年科学基金面上项目(81102896);
黑龙江省自然科学基金联合引导项目(LH2019H056);
中国博士后科学基金项目(2017M621319)。
通讯作者:
▲通讯作者
作者简介 : 南洋(1983.2-),女,博士,黑龙江中医药大学博士后流动站在站人员;研究方向:中药有效成分及机制。
[1] 朱其荣,喻雪琴,陈芳,等.信号传导通路在肝纤维化发生机制中的研究进展[J].山东医药,2019,59(11):109-112.
[2] 康艳敏,叶俊松,邹征伟,等.间充质干细胞在肝纤维化治疗中的研究进展[J].赣南医学院学报,2021,41(1):71-77.
[3] Ramachandran P,Dobie R,Wilson-Kanamori JR,et al. Resolving the fibrotic niche of human liver cirrhosis at single-cell level [J]. Nature,2019,575(7783):512-518.
[4] Williamson T,Sultanpuram N,Sendi H. The role of liver microenvironment in hepatic metastasis [J]. Clin Transl Med,2019,8(1):21-27.
[5] Carson JP,Ramm GA,Robinson MW,et al. Schistosome-induced Fibrotic Disease:The Role of Hepatic Stellate Cells [J]. Trends Parasitol,2018,34(6):524-540.
[6] Park H,Lee E,Kim Y,et al. Metabolic Profiling Analysis Reveals the Potential Contribution of Barley Sprouts against Oxidative Stress and Related Liver Cell Damage in Habitual Alcohol Drinkers [J]. Antioxidants(Basel),2021, 10(3):459-473.
[7] Louvet A,Mathurin P. Alcoholic liver disease:mechanisms of injury and targeted treatment [J]. Nat Rev Gastroenterol Hepatol,2015,12(4):231-242.
[8] Yuan SL,Dong M,Zhang HL,et al. Oral delivery of a Lactococcus lactis expressing extracellular TGFβR2 alleviates hepatic fibrosis [J]. Appl Microbiol Biotechnol,2021,105(14/15):6007-6018.
[9] Tsay HC,Yuan Q,Balakrishnan A,et al. Hepatocyte-specific suppression of micro RNA-221-3p mitigates liver fibrosis [J]. J Hepatol,2019,70(4):722-734.
[10] 付洪彦,龚作炯.肝纤维化的发生机制及其诊疗研究进展[J].中西医结合肝病杂志,2018,28(2):125-128.
[11] Sini?觢a ■,Sne?觩ana P,Ilijana G,et al. Effects of C60 Fullerene on Thioacetamide-Induced Rat Liver Toxicity and Gut Microbiome Changes [J]. Antioxidants(Basel),2021,10(6):911.
[12] Bashandy SAE,Alaamer A,Moussa SAA,et al. Role of zinc oxide nanoparticles in alleviating hepatic fibrosis and nephrotoxicity induced by thioacetamide in rat [J]. Can J Physiol Pharmacol,2017,96(4):337-344.
[13] Algandaby MM,Breikaa RM,Eid BG,et al. Icariin protectsagainst thioacetamide-induced liver fibrosis in rats:implication of anti-angiogenic and anti-autophagic properties [J]. Pharmacol Rep,2017,69(4):616-624.
[14] Ayd?覦n MM,Ak?觭al?覦 KC. Liver fibrosis [J]. Turk J Gastroenterol,2018,29(1):14-21.
[15] Cheng Y,Mai JY,Wang MF,et al. Antifibrotic effect of total flavonoids of Astmgali Radixon dimethylnitrosamine-induced liver cirrhosis in rats [J]. Chin J Integr Med,2017,23(1):48-54.
[16] Ding YF,Wu Zh,Wei YJ,et al. Hepatic inflammation-fibrosis-cancer axis in the rat hepatocellular carcinoma induced bydiethylnitrosamine [J]. J Cancer Res Clin Oncol,2017,143(5):821-834.
[17] 李志超,曹庆生,吴卫.矮地茶黄酮抗二甲基亚硝胺诱导大鼠肝纤维化作用及机制研究[J].中兽医医药杂志,2019,38(2):17-21.
[18] 华晓萍,赵科,唐大轩,等.肝宝胶囊调控巨噬细胞亚型构成逆转肝纤维化作用机理研究[J].中药药理与临床,2021,37(1):153-160.
[19] Jing ZH,Li HG,Cai YL,et al. Mice Lacking Adenosine 2A Receptor Reveal Increased Severity of MCD-induced NASH [J]. J Endocrinol,2019,243(3):199-209.
[20] Mridha AR,Wree A,Robertson AAB,et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis inmexperimental NASH in mice [J]. J Hepatol,2017,66(5):1037-1046.
[21] Li XY,Wang TX,Huang XM,et al. Targeting ferroptosis alleviates methionine-choline deficient(MCD)-diet induced NASH by suppressing liver lipotoxicity [J]. Liver Int,2020,40(6):1378-1394.
[22] Kristen S,Kennedy L,Laura H,et al. Updates on Dietary Models of Nonalcoholic Fatty Liver Disease:Current Studies and Insights [J]. Gene Expr,2018,18(1):5-17.
[23] 蔡江帆,陈民利.非酒精性脂肪肝炎动物模型的研究概况[J].中国实验动物学报,2021,29(1):128-136.
[24] Lin HY,Wang FS,Yang YL,et al. MicroRNA-29a Suppresses CD36 to Ameliorate High Fat Diet-Induced Steatohepatitis and Liver Fibrosis in Mice [J]. Cells,2019,8(10):1298-1315.
[25] 位小杰,刘东璞,贾诗慧.大黄酸联合红景天对肝纤维化大鼠治疗作用的研究[J].黑龙江医药科学,2021,44(2):65-67.
[26] Bao YL,Wang L,Pan HT,et al. Animal and Organoid Models of Liver Fibrosis [J]. Front Physiol,2021,12:666138.
[27] Zisser A,Ipsen DH,Pernille TN. Hepatic Stellate Cell Activation and Inactivation in NASH-Fibrosis-Roles as Putative Treatment Targets?[J]. Biomedicines,2021,9(4):365-383.
[28] 蔡宗余,李政.非酒精性脂肪肝病小鼠模型的研究进展[J].聊城大学学报(自然科学版),2021,34(1):95-103.
[29] Handa P,Maliken BD,Nelson JE,et al. Reduced adipon-ectin signaling due to weight gain results in nonal-coholic steatohepatitis through impaired mitochondrial biogenesis [J]. Hepatology,2014,60(1):133-145.
[30] 刘欣,齐永芬,鱼艳荣.血吸虫病肝纤维化中可溶性虫卵抗原对肝星状细胞的作用[J].中国寄生虫学与寄生虫病杂志,2019,37(2):218-222.
[31] 陈岩勤,高秀丽,诸葛洪祥,等.白头翁皂苷抗小鼠血吸虫病肝纤维化的试验[J].安徽农业科学,2019,47(14):181-182,200.
[32] 孔庆明,戴方伟,丁豪杰,等.青蒿琥酯抗小鼠血吸虫性肝纤维化的作用[J].中国药理学通报,2019,35(6):854-858.
[1]
曾祥荣1 李泰贤2 陈卫衡3. 基于股骨头坏死动物模型CiteSpace知识图谱的30年可视化分析 [J]. 中国医药导报, 2022, 19(8): 21-24,29.
[2]
吴小溪 汪涛 杜晟楠 蒋元烨▲ 曹勤▲. 7种无创诊断模型对慢性乙型肝炎肝纤维化及肝硬化的诊断价值评估 [J]. 中国医药导报, 2022, 19(10): 14-19.
[3]
潘富珍 刘定. 从活血通络法探讨川芎嗪抗肝纤维化的作用机制研究进展 [J]. 中国医药导报, 2021, 18(8): 34-37.
[4]
唐小勇 何斌. 脊柱椎间融合动物模型研究进展 [J]. 中国医药导报, 2021, 18(8): 38-41.
[5]
庞秋琳1 王振常2. 肝纤维化与线粒体自噬miR-135a/FOXO1/PINK1调节轴的研究进展 [J]. 中国医药导报, 2021, 18(36): 57-60.
[6]
黄大伟1 陆定波1 江诗怡1 李瀚旻2. 补肾生髓成肝方加减联合聚乙二醇干扰素α-2b治疗慢性乙型肝炎的效果及对患者肝功能及肝纤维化的影响 [J]. 中国医药导报, 2021, 18(34): 86-90.
[7]
李巍 王娇 苏莉▲ 苗劲蔚 吴玉梅. 卵巢癌异种移植动物模型的建立及鉴定研究 [J]. 中国医药导报, 2021, 18(32): 18-21.
[8]
温欣 张琪▲. 高血压病实验动物模型的应用概况与评价 [J]. 中国医药导报, 2021, 18(17): 36-39.
[9]
郑凇杨1,2 刘婷婷1,2 孙芳玲1,2 郑文荣1,2 祝自新1,2 郑瑞芳3 邢建国3 王文1,2,3,4. 手术致脑损伤的基础研究进展 [J]. 中国医药导报, 2021, 18(15): 37-40.
[10]
李怡佳 边艳超 李硕 肖瑞. 男性不育实验动物模型建立的研究进展 [J]. 中国医药导报, 2021, 18(15): 41-44,48.
[11]
王华1 杨柳明1 黄玲1 信洪武2 赵延龙1 许俊考1 黄春荣1 冯广贵1. 强肝胶囊治疗慢性乙型肝炎的临床效果 [J]. 中国医药导报, 2021, 18(10): 80-83.
[12]
陈俊名1 岳辰2 范亚楠2 何沛霖1 王会超2 刘又文2. 股骨头坏死动物造模研究进展 [J]. 中国医药导报, 2020, 17(9): 25-28.
[13]
王子恺* 毛泳彬* 孔力 钟星 孙晓雯 吴丹 袁晓环. 姜黄素及其类似物抑制CCl4诱导大鼠肝纤维化的作用及机制研究 [J]. 中国医药导报, 2020, 17(8): 13-16.
[14]
雷宇 曾清 程纬民. 非输血依赖型地中海贫血患者的标本论治 [J]. 中国医药导报, 2020, 17(5): 133-136.
[15]
宋净洋1 车祥源1 邢红霞2. 帕金森病的非人灵长类动物模型研究进展 [J]. 中国医药导报, 2020, 17(32): 44-47.