基于原发性肝癌临床病症特点的动物模型分析
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摘要
基于原发性肝癌的中西医临床病症特点,提出原发性肝癌动物模型评价标准。列出中西医原发性肝癌的临床表现和诊断标准,符合西医临床诊断标准1项赋值为11.1%,中医临床中符合1种证型赋值为12.5%,根据该标准对现有原发性肝癌动物模型进行评分,以评分反应动物模型与中西医临床病症特点的吻合情况,评分越高,吻合度越高。较高吻合度的动物模型制备方法有:移植性VX2兔肝癌动物模型和中医脾虚证、湿热证分别结合瘤细胞注射的大鼠动物模型,但存在诸多缺点。整体上原发性肝癌造模方法诸多,但缺少反应原发性肝癌临床特点和体现中医病因病证的动物模型,缺乏动物模型评价指标体系。完善原发性肝癌动物模型评价标准及建立体现原发性肝癌中西医临床病证特点的病理模型是未来研究的重点。
Based on the clinical characteristics of primary carcinoma of liver, the evaluation criteria of animal model of primary carcinoma of liver were proposed. The clinical manifestations and diagnosis criteria of primary carcinoma of liver in Chinese and Western medicine were listed. The value of 1 assignment accorded with the clinical diagnosis criteria of Western medicine was 11.1%, and that of 1 syndrome type accorded with 12.5% in Chinese medicine. According to this criterion, existing animal models of primary carcinoma of liver were scored to reflect the anastomosis between the animal models and the clinical symptoms of traditional Chinese medicine and Western medicine. The higher the score, the higher the anastomosis. The methods for the preparation of the animal models with higher anastomosis included: the animal model of transplantable VX2 rabbit liver cancer, the rat model of traditional Chinese medicine combined with spleen-deficiency syndrome and dampness-heat syndrome and tumor cell injection, but there are many shortcomings. On the whole, there are many ways to establish primary carcinoma of liver models, but there is lack of animal models reflecting the clinical characteristics of primary carcinoma of liver and the etiology and syndrome of TCM. It is the key for future research to improve the evaluation criteria of animal models of primary carcinoma of liver and to establish the pathological models reflecting the characteristics of clinical symptoms of primary carcinoma of liver of TCM and western medicine.
Based on the clinical characteristics of primary carcinoma of liver, the evaluation criteria of animal model of primary carcinoma of liver were proposed. The clinical manifestations and diagnosis criteria of primary carcinoma of liver in Chinese and Western medicine were listed. The value of 1 assignment accorded with the clinical diagnosis criteria of Western medicine was 11.1%, and that of 1 syndrome type accorded with 12.5% in Chinese medicine. According to this criterion, existing animal models of primary carcinoma of liver were scored to reflect the anastomosis between the animal models and the clinical symptoms of traditional Chinese medicine and Western medicine. The higher the score, the higher the anastomosis. The methods for the preparation of the animal models with higher anastomosis included: the animal model of transplantable VX2 rabbit liver cancer, the rat model of traditional Chinese medicine combined with spleen-deficiency syndrome and dampness-heat syndrome and tumor cell injection, but there are many shortcomings. On the whole, there are many ways to establish primary carcinoma of liver models, but there is lack of animal models reflecting the clinical characteristics of primary carcinoma of liver and the etiology and syndrome of TCM. It is the key for future research to improve the evaluation criteria of animal models of primary carcinoma of liver and to establish the pathological models reflecting the characteristics of clinical symptoms of primary carcinoma of liver of TCM and western medicine.
引文
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[19]张露蓉,姚霏,江国荣,等.玉屏风散直接抑制和免疫调节抗肝细胞癌作用的实验研究.中华中医药学刊,2014,32(5):1046-1050
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[22]ChenG,DaiZK,LiangRG,etal.Characterizationof diethylnitrosamine-induced liver carcinogenesis in Syrian golden hamsters.Exp Ther Med,2012,3(2):285-292
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[24]柴红涛,唐恩奇,李滨,等.N-亚硝基二乙胺(DEN)诱导SD大鼠肝癌模型的研究.安徽医学,2016,37(4):383-385
[25]蔡林雪,刘澍楠.半枝莲提取物对黄曲霉素B-1所诱发肝癌Notch1的影响.世界中医药,2015,10(1):83-85
[26]郑海平.银杏叶提取物对AFB1致大鼠肝癌抑制作用的研究.南宁:广西医科大学,2012
[27]赵鲁笳,刘小北,郭宏伟.3’-Me-DAB诱发大鼠肝癌模型的建立与病理研究.中国实验诊断学,2004,8(3):243-245
[28]朱建思,周建国.二甲基氨基偶氮苯诱发大鼠实验性肝癌的癌前期病理研究.衡阳医学院学报,1990,18(4):336-341,431-433
[29]宁宗,王乃平,臧林泉,等.二甲基氨基偶氮苯对肝脏和大脑组织中CYP2D1基因表达的影响.实用癌症杂志,2003,18(1):13-15
[30]范洁,张磊,王啸.人参皂苷Rk3对肝癌Hep G2细胞凋亡的影响.安徽医科大学学报,2016,51(11):1604-1608
[31]刘春佳,张星宇,单智焱,等.人肝癌Hep G2细胞小鼠荷瘤模型的建立及免疫耐受的探讨.中国民康医学,2015,27(14):152
[32]赵建夫,赵凤芝,陈文慧,等.CIK细胞联合贝伐单抗对肝癌HepG2细胞的体内外抗瘤活性.中国肿瘤生物治疗杂志,2017,24(4):404-410
[33]吴越,梁长虹,杨本强,等.兔VX2肝癌模型应用索拉非尼前后的CT灌注成像与组织学对照研究.中国临床医学影像杂志,2010,21(6):401-40
[34]杜童,韩琳,牛洪欣,等.兔VX2肝癌模型制作改良及影像学评价.中国比较医学杂志,2014,24(2):29-32
[35]童敏,陈柱.以改良方法建立兔VX2肝癌模型.中国组织工程研究,2015,19(27):4361-4364
[36]濮文渊,孙松娴,樊圣丽,等.肿瘤细胞接种数对建立小鼠肝癌移植瘤模型的影响.辽宁中医杂志,2016,43(9):1994-1996,2018
[37]王建,白明东,许刚.树突状细胞-Walker-256融合瘤苗的构建及对肝癌大鼠抗肿瘤作用的研究.中国普外基础与临床杂志,2011,18(5):507-513
[38]陈颖华,蔡常洁,陆敏强,等.建立符合肝癌肝移植术后肝癌复发规律的大鼠模型.中山大学学报(医学科学版),2006,27(6):640-643
[39]张火俊,陈栋,田建明,等.B超引导下大鼠种植性肝癌模型的建立.中国医学计算机成像杂志,2005,11(2):122-124
[40]李琦,刘宣.肿瘤中医证候动物模型研究的现状概述.中医杂志,2010,51(11):1041-1044
[41]沈莹莹,谷建钟,郭勇.脾虚证荷瘤小鼠比较性治疗的实验研究.浙江中医杂志,2015,50(3):174-175
[42]陈燕,项婷,孙保国,等.脾虚小鼠原位移植肝癌模型的建立及评价.中西医结合肝病杂志,2016,26(1):30-31,47
[43]张德春,杨传标,张曼,等.实验性大鼠肝癌脾虚证和湿热证主要肝功能指标的对比研究.湖南中医杂志,2006,22(6):79-80
[44]杨传标,张曼,王红,等.大鼠肝癌湿热证、脾虚证与野生型p53 mRNA、N-ras表达相关性研究.南方医科大学学报,2007,27(11):1738-1739,1742
[45]He L,Tian D A,Li P Y,et al.Mouse models of livers of liver caner:Progress and recommendations.On cotarget,2015,6(27):23306-23322
[2]王述莲,呼建民,何光伦,等.血清肿瘤标志物联合血常规指标检测在原发性肝癌诊断中的应用研究标记免疫分析与临床,2017,24(1):4-7
[3]汤钊猷.现代肿瘤学.上海:复旦大学出版社,2014:891-934
[4]Bruix J,Sherman M.American association for the study of liver diseases.Management of hepatocellular carcinoma:an update.Hepatology,2011,53(3):1020-1022
[5]Zhu P L,Yin C,Feng J L.The recent advances in the treatment of primary liver cancer comprehensive.J Clin Hepatol,2015,31(6):965-968
[6]李亚杰,彭成,张吉仲.病证结合肝癌动物模型研究现状.四川动物,2009,28(3):448-449
[7]付珍娜,王婷,白明,等.基于中西医临床病症特点的痤疮动物模型分析.中国中药杂志,2018,43(6):1288-1291
[8]曹利华,苗明三.基于围绝经期抑郁症临床病症特点的动物模型分析.中华中医药杂志,2016,31(5):1643-1647
[9]田硕,白明,苗明三.基于围绝经期综合征临床病症特点的动物模型分析.中国实验方剂学杂志,2015,21(19):217-221
[10]刘星.原发性肝癌病因与其临床表现分析.大家健康(学术版),2013,7(22):147
[11]邱钰芹,袁立霞,陈世贤,等.试述原发性肝癌的病因病机.光明中医,2014,29(2):354-355
[12]吴孟超,汤钊猷,刘彤华,等.原发性肝癌规范化病理诊断指南(2015年版).临床肝胆病杂志,2015,(6):833-839
[13]中国抗癌协会肝癌专业委员会.原发性肝癌诊断标准.中华肝脏病杂志,2000,(3):135
[14]原发性肝癌影像学诊断标准.临床医学影像杂,1991,2(4):216-218
[15]中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范(2017年版).传染病信息,2017,30(3):111-127
[16]Yu S J,Kim H,Min H,et al.Targeted proteomics predicts asustained complete-response after transarterial chemoembolization and clinical outcomes in patients with hepatocelluar carcinoma:a prospective cohort study.J Proteome Res,2017,16(3):1239-1248
[17]Kohla M A,Abu Zeid Ml,Al-Warraky M,et al.Predictors of hepatic decompensation after TACE for hepatocelluar carcinoma.BMJ Open Gasroenterol,2015,2(1):1-9
[18]龙顺钦,杨小兵,吴万垠,等.原发性肝癌的中医体质类型分布及其预后因素分析.中国肿瘤临床,2012,29(2):101-104
[19]张露蓉,姚霏,江国荣,等.玉屏风散直接抑制和免疫调节抗肝细胞癌作用的实验研究.中华中医药学刊,2014,32(5):1046-1050
[20]凌昌全,刘庆,李东涛,等.原发性肝癌常见中医基本证候定性诊断规范的研究.中西医结合学报,2005,3(2):95-98
[21]French D M,Lin B C,Wang M,et al.Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models.PLoS One,2012,7(5):e36713
[22]ChenG,DaiZK,LiangRG,etal.Characterizationof diethylnitrosamine-induced liver carcinogenesis in Syrian golden hamsters.Exp Ther Med,2012,3(2):285-292
[23]谢胜学,许戈良,荚卫东,等.二乙基亚硝胺联合N-亚硝基吗啉诱导大鼠肝癌模型的实验病理研究.肝胆外科杂志,2008,16(2):135-137
[24]柴红涛,唐恩奇,李滨,等.N-亚硝基二乙胺(DEN)诱导SD大鼠肝癌模型的研究.安徽医学,2016,37(4):383-385
[25]蔡林雪,刘澍楠.半枝莲提取物对黄曲霉素B-1所诱发肝癌Notch1的影响.世界中医药,2015,10(1):83-85
[26]郑海平.银杏叶提取物对AFB1致大鼠肝癌抑制作用的研究.南宁:广西医科大学,2012
[27]赵鲁笳,刘小北,郭宏伟.3’-Me-DAB诱发大鼠肝癌模型的建立与病理研究.中国实验诊断学,2004,8(3):243-245
[28]朱建思,周建国.二甲基氨基偶氮苯诱发大鼠实验性肝癌的癌前期病理研究.衡阳医学院学报,1990,18(4):336-341,431-433
[29]宁宗,王乃平,臧林泉,等.二甲基氨基偶氮苯对肝脏和大脑组织中CYP2D1基因表达的影响.实用癌症杂志,2003,18(1):13-15
[30]范洁,张磊,王啸.人参皂苷Rk3对肝癌Hep G2细胞凋亡的影响.安徽医科大学学报,2016,51(11):1604-1608
[31]刘春佳,张星宇,单智焱,等.人肝癌Hep G2细胞小鼠荷瘤模型的建立及免疫耐受的探讨.中国民康医学,2015,27(14):152
[32]赵建夫,赵凤芝,陈文慧,等.CIK细胞联合贝伐单抗对肝癌HepG2细胞的体内外抗瘤活性.中国肿瘤生物治疗杂志,2017,24(4):404-410
[33]吴越,梁长虹,杨本强,等.兔VX2肝癌模型应用索拉非尼前后的CT灌注成像与组织学对照研究.中国临床医学影像杂志,2010,21(6):401-40
[34]杜童,韩琳,牛洪欣,等.兔VX2肝癌模型制作改良及影像学评价.中国比较医学杂志,2014,24(2):29-32
[35]童敏,陈柱.以改良方法建立兔VX2肝癌模型.中国组织工程研究,2015,19(27):4361-4364
[36]濮文渊,孙松娴,樊圣丽,等.肿瘤细胞接种数对建立小鼠肝癌移植瘤模型的影响.辽宁中医杂志,2016,43(9):1994-1996,2018
[37]王建,白明东,许刚.树突状细胞-Walker-256融合瘤苗的构建及对肝癌大鼠抗肿瘤作用的研究.中国普外基础与临床杂志,2011,18(5):507-513
[38]陈颖华,蔡常洁,陆敏强,等.建立符合肝癌肝移植术后肝癌复发规律的大鼠模型.中山大学学报(医学科学版),2006,27(6):640-643
[39]张火俊,陈栋,田建明,等.B超引导下大鼠种植性肝癌模型的建立.中国医学计算机成像杂志,2005,11(2):122-124
[40]李琦,刘宣.肿瘤中医证候动物模型研究的现状概述.中医杂志,2010,51(11):1041-1044
[41]沈莹莹,谷建钟,郭勇.脾虚证荷瘤小鼠比较性治疗的实验研究.浙江中医杂志,2015,50(3):174-175
[42]陈燕,项婷,孙保国,等.脾虚小鼠原位移植肝癌模型的建立及评价.中西医结合肝病杂志,2016,26(1):30-31,47
[43]张德春,杨传标,张曼,等.实验性大鼠肝癌脾虚证和湿热证主要肝功能指标的对比研究.湖南中医杂志,2006,22(6):79-80
[44]杨传标,张曼,王红,等.大鼠肝癌湿热证、脾虚证与野生型p53 mRNA、N-ras表达相关性研究.南方医科大学学报,2007,27(11):1738-1739,1742
[45]He L,Tian D A,Li P Y,et al.Mouse models of livers of liver caner:Progress and recommendations.On cotarget,2015,6(27):23306-23322