原位膀胱肿瘤动物模型构建及活体检测体系研究  

Construction and living body detection system of orthotopic models of urinary bladder cancer

作　　者：许天源[1] 朱照伟[1] 王先进[1] 夏磊磊[1] 秦亮[1] 张祥[1] 钟山[1] 张敏光[1] 沈周俊[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院泌尿外科,200025

出　　处：《中华实验外科杂志》2015年第12期3196-3200,共5页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（81472379）;上海市科委实验动物研究领域科技支撑项目（12140901201）

摘　　要：目的比较不同方法诱导大鼠原位膀胱肿瘤的模型特点，探索建立活体检测体系。方法将50只sD大鼠随机分为3组：甲组（20只）为N-甲基亚硝基脲（MNU）造模组，每两周予膀胱灌注MNU溶液0．1ml（0．2mg），共4次；乙组（20只）为N-正丁基-N-（4-羟丁基）亚硝胺（BBN）造模组，给予0．05％BBN溶液连续喂养8周；丙组（10只）为对照组，予甲组同法膀胱灌注枸橼酸缓冲液0．1ml。3组大鼠造模诱导期后均常规饲养，观察-般症状体征。22周时，利用超声、核磁共振（MR）和计算机断层扫描（CT）等方法对存活大鼠成瘤情况进行活体检测；其中CT平扫前辅以碘造影剂膀胱灌注，三维重建以进行大鼠尿路成像（CTU）。活体检测完成后处死所有大鼠，取膀胱组织进行病理组织学观察。分析大鼠原位膀胱肿瘤的模型特点，比较不同活体检测方法的鉴定效果。结果甲组大鼠死亡5只，原因包括麻醉过量、感染和恶病质；乙组死亡6只，可能因药物肝肾毒性所致。22周时成瘤率甲组94％，乙组71％。与乙组比较，甲组膀胱肿瘤体积更大、浸润范围更广，光镜下肿瘤细胞异型更明显，多见肌层浸润。超声、MR和改良CT对成瘤大鼠检出率分别为96．0％、62．5％和100％；大鼠膀胱在CTU下得到立体呈现，原位肿瘤大小、边界、定位清晰。结论通过比较学研究，明确了不同大鼠原位膀胱肿瘤诱导方法的安全性、建模效果及病理特征，并建立r包括超声、MR、CT和CTU在内的活体检测体系。Objective To compare model features of rat orthotopic bladder cancer induced using different methods, and to establish the living body detection system. Methods Fifty SD rats were random- ly divided into 20 of group A （ orthotopic bladder cancer induced by N - methyl - nitrosourea, MNU） , 20 of group B （induced by N - butly - N -4 - hydroxybutyl - nitrosamine, BBN） and 10 of group C （ con- trol）. In group A, each rat was administered with intravesical instillation of 0. 1 ml MNU solution （0. 2 mg） every other week, totally four times. In group B, each rat was given drinking water containing 0. 05% BBN for consecutive eight weeks. In group C, each rat was treated with 0. 1 ml citrate buffer solution ac- cording the same regimen with group A. After induction, all groups were routinely fed and general states were recorded. At the 22nd week, living body detection of orthotopic tumor formation was performed using ultrasound （ US）, magnetic resonance （MR） and computed tomography （CT） scanning. Specifically, all rats received intravesical instillation of omnipaque solution before scanning and CT urography （CTU） was acquired from 3D reconstruction of CT images. After living body detection, all rats were sacrificed for blad- der pathological examination. Model features of bladder cancer were analyzed, and efficacies of different imaging modalities were compared. Results There were five rats dying of overdose anesthesia, infection and cachexia in group A. In contrast, six died in group B and the reason should be BBN - induced dama- ges in hepatic and renal functions. At the 22nd week, proportions of tumor bearing rats were 94% for group A and 71% for group B, respectively. Compared to the group B, neoplasms in group A were larger and spread more widely, showing higher cellular atypia and muscular invasion microscopically. Sensitivities of living body detection of orthotopic tumor formation were 96. 0% for US, 62. 5% for MR and 100% for modified CT. The 3D image of rat bladder was presented w

关 键 词：膀胱癌 动物模型 N-甲基亚硝基脲 N-正丁基-N-(4-羟丁基)亚硝胺 超声 核磁共振 计算机断层扫描 活体检测 

分 类 号：R816.8[医药卫生—放射医学]