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