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兔VX2肝癌动物模型的建立

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2024年6月6日发(作者:偶玉)

第25卷第2期 

川北医学院学报 

VoI.25.No.2 

156 

2010年4月 JOURNAL OF N0RTH SICHUAN MEDICAL COLLEGE 

Apr.2010 

兔VX2肝癌动物模型的建立术 

杨林。,李祖茂 ,周翔平 

(1.川北医学院附属医院放射科,I ̄t)tI南充637000;2.JII北医学院附属医院病理科,四川南充637000;3.四川大学华西 

医院放射科,四川成都610041) 

【摘要】目的:介绍应用VX2肿瘤组织块制作兔移植性肝癌模型方法。方法:新西兰大白兔26只,采用开腹瘤块包埋法 

接种兔VX2瘤于肝左叶。于移植后2—3周进行CT扫描及数字减影血管造影(diagnostic digital subtraction angiography, 

DSA),实验完成后处死实验兔进行病理学检查。结果:26只兔均接种成功,接种成功率100%。VX2肝癌在CT平扫呈低密 

度,在肝动脉期表现为不同程度的环形强化,在门脉期呈低密度,病灶与周围肝组织分界清楚。肝动脉数字减影血管造影可 

见肿瘤染色。结论:兔VX2肝癌的表现与人类原发性肝癌类似,是肝癌介入治疗实验研究的理想动物模型。 

【关键词】动物实验;兔;肝癌;螺旋CT;介入放射学 

【文章编号】1005.3697(2010)02-0156-04【中图分类号】R815 【文献标识码】A 

Establishment of a VX2 Hepatic Cancer Model in Rabbits 

YANG Lin ,LI Zu・mao ,ZHOU Xiang—ping 

(1.Department ofRadiology,the Afifliated Hospital,North Sichuan Medical College,Nanchong 637000,China;2.Department foPa- 

thology,the Afifliated Hospital,North Sichuan Medical College,Nanchong 637000,China;3.Department foRadioolgy,West China 

Hospital,Sichuang University,Chengdu 610041,China) 

【Abstract】Objective:To introduce the establishment of a VX2 hepatic cancer model in rabbits.Methods:Twenty—six New Zealand 

white rabbits were implanted with VX2 tumor in the left lobe of the liver.CT scanning and digital subtraction angiography(DSA)were 

performed in all the rabbits 2 to 3 weeks after implantation.Results:All the twenty—six(100%)rabbits were successfully implanted 

with VX2 tumor in the liver.The tumors were demonstrated as hypodensity on plain CT images,tinge—enhanced on arterial phase ima- 

ges and hypodensity on portal phase images.Digital subtraction angiography of the hepatic artery confirmed the hypervascular mass with 

tumor vasculature.Conclusion:The VX2 hepatic tumors in rabbits demonstrate their hemodynamics as human primary hepatic carcino- 

mas,and it is more suitable for interventional experimental study. 

【Key words】Animal experiment;Rabbit;Liver cancer;Helical computed tomography;Interventional radiology 

原发性肝癌(primary hepatic carcinoma,PHC) 

率低等缺点。另外,采用大鼠肝癌动物模型进行数 

的发病率在世界各地均呈上升趋势,也是我国常见 

字减影血管造影(diagnostic digital subtraction angi・ 

的恶性肿瘤之一。PHC手术切除率仅20%,在PHC ography,DSA)及肝动脉化疗栓塞(chemoemboliza— 

的非手术疗法中,介人治疗占有及其重要的地位。 tion)治疗的研究多需开腹行肝动脉插管,操作较为 

如何提高肝癌介入治疗的远期疗效仍是临床面临的 复杂,动物死亡率较高。兔VX2肿瘤是由Shope 

重要课题。肝癌介入治疗的实验研究需要借助动物 

等¨ 使用病毒在兔皮肤诱导出的乳头状瘤,经72次 

模型来完成。既往肝癌动物模型多采用化学药物诱 传代培养后,建立起来的鳞癌细胞株。由于兔缺乏 

导法建立在大鼠身上,该法具有诱导时间长和成瘤 针对该肿瘤的抗体,故此鳞癌极易在兔体内生长,常 

接种到兔的肝脏和肾脏等部位,制作原位肿瘤模型。 

基金项目:四川省科技厅项目(2008JY0088—2) 

作者简介:杨林(1965一),男,四川武胜人,医学博士,副教 

本文介绍应用VX2肿瘤组织块制作兔移植性肝癌 

授,主要从事腹部影像诊断与介入治疗的基础 

模型方法。 

与临床研究。 

收稿日期:2009一l2—14 

第25卷第2期 

川北医学院学报 

V01.25.N0.2 

2010年4月 

JOURNAL OF NORTH SICHUAN MEDICAL COLLEGE 

Apr・2010 159 

的血流量(blood flow,BF)、血容量(blood volume, 

BV)和表面通透性(permeability surface,PS)均高于 

正常肌肉组织,而平均通过时间(mean transit time, 

MTr)低于正常肌肉组织。Kapanen等 采用CT 

灌注成像研究5只新西兰大白兔VX2肝癌,发现兔 

VX2肝癌的动脉灌注量显著高于正常肝脏的动脉 

灌注量,而门静脉灌注量显著低于正常肝脏的门静 

脉灌注量。杨林等 u采用CT灌注成像技术对比研 

究1O例兔VX2肝癌和8例正常兔(对照组)血流灌 

注差异,发现兔VX2肝癌肝动脉灌注量(hepatic ar- 

terial perfusion,HAP)和肝动脉灌注指数(hepatic 

a ̄efial perfusion index,HAPI)高于对照组;门静脉 

灌注量(hepatic po ̄al perfusion,HPP)、总肝灌注量 

(total liver perfusion,TLP)和门静脉灌注指数(he. 

parle portal perfuiosn index,HPPI)低于对照组。以 

上研究表明兔VX2肝癌是主要由肝动脉供血的富 

血供肿瘤,与人类PHC血流动力学特点相似,是 

PHC介入治疗实验研究的理想动物模型。 

【参考文献】 

[I] 

Shop RE,Hurst EW.Infectious papillomatosis of rabbits:with a 

note on the histopathology[J].J Exp Med,1933,58(5):607— 

624 

[2] 

Kapanen MK。Halavaara JT,Hakkinen AM.Assessment of vaseu・ 

lar physiology of tumorous livers:comparison of two diferent meth- 

dos[J].Acad Radiol,2003,i0(9):1021—1029 

[3] 

Lin WY。Chen J,Lin Y,et a1.Implantation of VX2 carcinoma 

into the liver of rabbits:a comparison of three direct・injection 

methods[J].J Vet Med Sci,2002,64(7):649—652 

[4] 

Tada Y,Tabuchi Y,Saito Y.Establishment of an experimental 

model with 8 higll frequency of liver metastasis and recurrence 

from gastirc VX2 cancer:histological analysis of the developmental 

process of primary and metastatic cancer lesions[J].Nippon Ge— 

ka Gakkai Zasshi,1992,93(8):818—826 

[5] 杨林,周翔平。官泳松,等.兔VX2肝癌MSCT评价及病理特 

征[J].中国医学影像技术,2007,23(4):623—625 

[6] 

Kim YI.Chung JW,Plrk JH。et a1.Intraarterial gene delivery in 

rabbit hepatic tumors:transfection with nonviarl vector by using io— 

dized oil emulsion[J].Radiology,2006,240(3):771—777 

[7] 

Maruyama H,Matsutani S,Saisho H,et a1.Sonographic shitf of 

hypervascular liver tumor on blood pool harmonic images with def- 

inity:time・related changes of contrast—enhanced appearance in 

rabbit VX2 tumor under extar-low acoustic power[J].Eur J Radi— 

ol,2005,56(1):60—65 

[8] 

Mitsumori M,Hiraoka M,Shibata T,et 1a.Targeted hyperthermia 

using dextran magnetite complex:a new teratment modality for liv- 

ertumors[J].Hepatogastorenterology,1996,43(12):1431— 

1437 

[9 J Kuszyk BS,Bluemke DA,Choti MA,et a1.Contarst—enhanced 

CT of small hypovascular hepatic tumors:effect of lesion enhance— 

ment on conspicuity in rabbits[J].AJR,2000,174(2):471— 

475 

[10]Kaneko A,Naomoto Y,Aoyama M。et a1.Tissue levels of ehemo. 

therapeutic agents for hepatic metastasis during hepatic arterial and 

portal injection[J].In vivo,1999,13(2):195—198 

[1 1]Miles KA,Hayball MP,Dixon AK.Functional images of hepatic 

perfusion obtained with dynamic CT[J].Radiology,1993,188 

(2):4o5—4¨ 

[12]Miles KA,Leggett DA,Kelley BB,et a1.In vivo assessment of 

neovascularization of liver metastases using perfusion CT[J].Br J 

Radiol,1998,71(843):276—281 

[13]Leggett DA,Kelley BB,Bunee IH,et a1.Colorectal cancer:di- 

agnostic potential of CT measurements of hepatic perfusion and im- 

plications for contarst enhancement protocols[J].Radiology, 

1997。205(3):716—720 

[14]Pandharipande PV。Krinsky GA,Rusinek H。et a1.Perfusion im. 

aging of the liver:current challenges and future goals[J】.Radi- 

ology,2005,234(3):661—673 

[15]Purdie TC。Henderson E,Lee TY.Functional CT imaging of an・ 

giogenesis in rabbit VX2 soft・tissue tumour[J].Phys MOd Biol。 

2001,46(12):3161—3175 

[16]Kapanen MK,Halavaara JT,Hakkinen AM.Open four-eompart— 

ment model in the measurement of liver perfusion[J].Acad Radi・ 

ol。2005,12(12):1542—1550 

[17]Halavaara JT。Hamberg LM,Leong FS,et a1.Functional CT with 

an experimental intravascular contrast agent in the assessment of 

liver vascular physiology[J].Acad Radiol,1996,3(11):946— 

952 

[18]Materne R,Van Beers BE,Smith AM,et a1.Non—invasive 

quantiifcation of liver perfusion with dynamic computed tomo・ 

graphy and a dual—input one—compartmental model[J].Clin Sci 

(Lond),2000,99(6):517—525 

[19]Zhang J,Wang R,Wang M,et a1.Experimental study of multi・ 

slice spiral CT perfusion imaging in VX2 soft-tissue tumor of rab- 

bits[J].J Huazhong Univ Sci Technolog Med Sci,2006,26(3): 

341—343 

[20]Kapanen MK.Halavaara JT,Hakkinen AM.Assessment of vascu- 

lar physiology of tumorous livers:comparison of two diferent moth— 

dos[J].Acad Radiol,2003,10(9):1021—1029 

[21]杨林,张小明,周翔平,等.兔VX2肝癌血流灌注的MDCT灌 

注成像评价[J].当代医学(中国介入放射学),2009,3(4): 

464—467 

2024年6月6日发(作者:偶玉)

第25卷第2期 

川北医学院学报 

VoI.25.No.2 

156 

2010年4月 JOURNAL OF N0RTH SICHUAN MEDICAL COLLEGE 

Apr.2010 

兔VX2肝癌动物模型的建立术 

杨林。,李祖茂 ,周翔平 

(1.川北医学院附属医院放射科,I ̄t)tI南充637000;2.JII北医学院附属医院病理科,四川南充637000;3.四川大学华西 

医院放射科,四川成都610041) 

【摘要】目的:介绍应用VX2肿瘤组织块制作兔移植性肝癌模型方法。方法:新西兰大白兔26只,采用开腹瘤块包埋法 

接种兔VX2瘤于肝左叶。于移植后2—3周进行CT扫描及数字减影血管造影(diagnostic digital subtraction angiography, 

DSA),实验完成后处死实验兔进行病理学检查。结果:26只兔均接种成功,接种成功率100%。VX2肝癌在CT平扫呈低密 

度,在肝动脉期表现为不同程度的环形强化,在门脉期呈低密度,病灶与周围肝组织分界清楚。肝动脉数字减影血管造影可 

见肿瘤染色。结论:兔VX2肝癌的表现与人类原发性肝癌类似,是肝癌介入治疗实验研究的理想动物模型。 

【关键词】动物实验;兔;肝癌;螺旋CT;介入放射学 

【文章编号】1005.3697(2010)02-0156-04【中图分类号】R815 【文献标识码】A 

Establishment of a VX2 Hepatic Cancer Model in Rabbits 

YANG Lin ,LI Zu・mao ,ZHOU Xiang—ping 

(1.Department ofRadiology,the Afifliated Hospital,North Sichuan Medical College,Nanchong 637000,China;2.Department foPa- 

thology,the Afifliated Hospital,North Sichuan Medical College,Nanchong 637000,China;3.Department foRadioolgy,West China 

Hospital,Sichuang University,Chengdu 610041,China) 

【Abstract】Objective:To introduce the establishment of a VX2 hepatic cancer model in rabbits.Methods:Twenty—six New Zealand 

white rabbits were implanted with VX2 tumor in the left lobe of the liver.CT scanning and digital subtraction angiography(DSA)were 

performed in all the rabbits 2 to 3 weeks after implantation.Results:All the twenty—six(100%)rabbits were successfully implanted 

with VX2 tumor in the liver.The tumors were demonstrated as hypodensity on plain CT images,tinge—enhanced on arterial phase ima- 

ges and hypodensity on portal phase images.Digital subtraction angiography of the hepatic artery confirmed the hypervascular mass with 

tumor vasculature.Conclusion:The VX2 hepatic tumors in rabbits demonstrate their hemodynamics as human primary hepatic carcino- 

mas,and it is more suitable for interventional experimental study. 

【Key words】Animal experiment;Rabbit;Liver cancer;Helical computed tomography;Interventional radiology 

原发性肝癌(primary hepatic carcinoma,PHC) 

率低等缺点。另外,采用大鼠肝癌动物模型进行数 

的发病率在世界各地均呈上升趋势,也是我国常见 

字减影血管造影(diagnostic digital subtraction angi・ 

的恶性肿瘤之一。PHC手术切除率仅20%,在PHC ography,DSA)及肝动脉化疗栓塞(chemoemboliza— 

的非手术疗法中,介人治疗占有及其重要的地位。 tion)治疗的研究多需开腹行肝动脉插管,操作较为 

如何提高肝癌介入治疗的远期疗效仍是临床面临的 复杂,动物死亡率较高。兔VX2肿瘤是由Shope 

重要课题。肝癌介入治疗的实验研究需要借助动物 

等¨ 使用病毒在兔皮肤诱导出的乳头状瘤,经72次 

模型来完成。既往肝癌动物模型多采用化学药物诱 传代培养后,建立起来的鳞癌细胞株。由于兔缺乏 

导法建立在大鼠身上,该法具有诱导时间长和成瘤 针对该肿瘤的抗体,故此鳞癌极易在兔体内生长,常 

接种到兔的肝脏和肾脏等部位,制作原位肿瘤模型。 

基金项目:四川省科技厅项目(2008JY0088—2) 

作者简介:杨林(1965一),男,四川武胜人,医学博士,副教 

本文介绍应用VX2肿瘤组织块制作兔移植性肝癌 

授,主要从事腹部影像诊断与介入治疗的基础 

模型方法。 

与临床研究。 

收稿日期:2009一l2—14 

第25卷第2期 

川北医学院学报 

V01.25.N0.2 

2010年4月 

JOURNAL OF NORTH SICHUAN MEDICAL COLLEGE 

Apr・2010 159 

的血流量(blood flow,BF)、血容量(blood volume, 

BV)和表面通透性(permeability surface,PS)均高于 

正常肌肉组织,而平均通过时间(mean transit time, 

MTr)低于正常肌肉组织。Kapanen等 采用CT 

灌注成像研究5只新西兰大白兔VX2肝癌,发现兔 

VX2肝癌的动脉灌注量显著高于正常肝脏的动脉 

灌注量,而门静脉灌注量显著低于正常肝脏的门静 

脉灌注量。杨林等 u采用CT灌注成像技术对比研 

究1O例兔VX2肝癌和8例正常兔(对照组)血流灌 

注差异,发现兔VX2肝癌肝动脉灌注量(hepatic ar- 

terial perfusion,HAP)和肝动脉灌注指数(hepatic 

a ̄efial perfusion index,HAPI)高于对照组;门静脉 

灌注量(hepatic po ̄al perfusion,HPP)、总肝灌注量 

(total liver perfusion,TLP)和门静脉灌注指数(he. 

parle portal perfuiosn index,HPPI)低于对照组。以 

上研究表明兔VX2肝癌是主要由肝动脉供血的富 

血供肿瘤,与人类PHC血流动力学特点相似,是 

PHC介入治疗实验研究的理想动物模型。 

【参考文献】 

[I] 

Shop RE,Hurst EW.Infectious papillomatosis of rabbits:with a 

note on the histopathology[J].J Exp Med,1933,58(5):607— 

624 

[2] 

Kapanen MK。Halavaara JT,Hakkinen AM.Assessment of vaseu・ 

lar physiology of tumorous livers:comparison of two diferent meth- 

dos[J].Acad Radiol,2003,i0(9):1021—1029 

[3] 

Lin WY。Chen J,Lin Y,et a1.Implantation of VX2 carcinoma 

into the liver of rabbits:a comparison of three direct・injection 

methods[J].J Vet Med Sci,2002,64(7):649—652 

[4] 

Tada Y,Tabuchi Y,Saito Y.Establishment of an experimental 

model with 8 higll frequency of liver metastasis and recurrence 

from gastirc VX2 cancer:histological analysis of the developmental 

process of primary and metastatic cancer lesions[J].Nippon Ge— 

ka Gakkai Zasshi,1992,93(8):818—826 

[5] 杨林,周翔平。官泳松,等.兔VX2肝癌MSCT评价及病理特 

征[J].中国医学影像技术,2007,23(4):623—625 

[6] 

Kim YI.Chung JW,Plrk JH。et a1.Intraarterial gene delivery in 

rabbit hepatic tumors:transfection with nonviarl vector by using io— 

dized oil emulsion[J].Radiology,2006,240(3):771—777 

[7] 

Maruyama H,Matsutani S,Saisho H,et a1.Sonographic shitf of 

hypervascular liver tumor on blood pool harmonic images with def- 

inity:time・related changes of contrast—enhanced appearance in 

rabbit VX2 tumor under extar-low acoustic power[J].Eur J Radi— 

ol,2005,56(1):60—65 

[8] 

Mitsumori M,Hiraoka M,Shibata T,et 1a.Targeted hyperthermia 

using dextran magnetite complex:a new teratment modality for liv- 

ertumors[J].Hepatogastorenterology,1996,43(12):1431— 

1437 

[9 J Kuszyk BS,Bluemke DA,Choti MA,et a1.Contarst—enhanced 

CT of small hypovascular hepatic tumors:effect of lesion enhance— 

ment on conspicuity in rabbits[J].AJR,2000,174(2):471— 

475 

[10]Kaneko A,Naomoto Y,Aoyama M。et a1.Tissue levels of ehemo. 

therapeutic agents for hepatic metastasis during hepatic arterial and 

portal injection[J].In vivo,1999,13(2):195—198 

[1 1]Miles KA,Hayball MP,Dixon AK.Functional images of hepatic 

perfusion obtained with dynamic CT[J].Radiology,1993,188 

(2):4o5—4¨ 

[12]Miles KA,Leggett DA,Kelley BB,et a1.In vivo assessment of 

neovascularization of liver metastases using perfusion CT[J].Br J 

Radiol,1998,71(843):276—281 

[13]Leggett DA,Kelley BB,Bunee IH,et a1.Colorectal cancer:di- 

agnostic potential of CT measurements of hepatic perfusion and im- 

plications for contarst enhancement protocols[J].Radiology, 

1997。205(3):716—720 

[14]Pandharipande PV。Krinsky GA,Rusinek H。et a1.Perfusion im. 

aging of the liver:current challenges and future goals[J】.Radi- 

ology,2005,234(3):661—673 

[15]Purdie TC。Henderson E,Lee TY.Functional CT imaging of an・ 

giogenesis in rabbit VX2 soft・tissue tumour[J].Phys MOd Biol。 

2001,46(12):3161—3175 

[16]Kapanen MK,Halavaara JT,Hakkinen AM.Open four-eompart— 

ment model in the measurement of liver perfusion[J].Acad Radi・ 

ol。2005,12(12):1542—1550 

[17]Halavaara JT。Hamberg LM,Leong FS,et a1.Functional CT with 

an experimental intravascular contrast agent in the assessment of 

liver vascular physiology[J].Acad Radiol,1996,3(11):946— 

952 

[18]Materne R,Van Beers BE,Smith AM,et a1.Non—invasive 

quantiifcation of liver perfusion with dynamic computed tomo・ 

graphy and a dual—input one—compartmental model[J].Clin Sci 

(Lond),2000,99(6):517—525 

[19]Zhang J,Wang R,Wang M,et a1.Experimental study of multi・ 

slice spiral CT perfusion imaging in VX2 soft-tissue tumor of rab- 

bits[J].J Huazhong Univ Sci Technolog Med Sci,2006,26(3): 

341—343 

[20]Kapanen MK.Halavaara JT,Hakkinen AM.Assessment of vascu- 

lar physiology of tumorous livers:comparison of two diferent moth— 

dos[J].Acad Radiol,2003,10(9):1021—1029 

[21]杨林,张小明,周翔平,等.兔VX2肝癌血流灌注的MDCT灌 

注成像评价[J].当代医学(中国介入放射学),2009,3(4): 

464—467 

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