摘要
目的探讨亚硝基二乙胺(DENA)诱发 SD 大鼠肝癌模型的方法,为肝癌影像诊断和介入治疗提供可靠的动物模型。方法浓度0.95g/L 的 DENA 水溶液供140只雄性 SD 大鼠自由饮用,10周后停止饮用此水溶液。第11周时行 MR 检查,以筛查大鼠肝脏肿瘤发病情况;首次影像检查结果阳性者进入后续处理,阴性者继续饲养、观察,并于4周后复查;其中64只大鼠于处死前行血管造影以了解肝肿瘤的血供情况;最后获得的组织标本按不同的目的分别保存备用,分别于光镜下和电镜下观察;并行免疫组织化学方法检测肿瘤源性和肿瘤标志物甲胎蛋白(AFP)的表达水平。结果肝脏成癌时间最早11.0周、最迟20.0周,中位成癌期13.9周,至20.0周末72只存活动物100%成癌;肝脏单发肿瘤占9.7%(7/72),多发占90.3%(65/72),多发者中有肝硬化背景者占87.7%(57/65);远处转移占18.1%(13/72);血管造影提示肝肿瘤血供丰富且以肝动脉供血为主;免疫组织化学检查证实肿瘤组织属于肝细胞源性,且肿瘤标志物 AFP 呈强阳性;光镜下鉴定组织学类型:肝细胞肝癌占92.0%(66/72),胆管细胞癌占4.0%(3/72),混合型占4.0%(3/72);电镜证实肿瘤细胞异型性明显,细胞器异常。结论 DENA 可诱发较理想的用于影像诊断和介入治疗研究的大鼠肝癌模型,MRI 是较简捷而有效的动态监测措施。
Objective To explore the feasible approach for establishment of a liver cancer model induced by N-nitrosodiethylamine （DENA） with Sprague-Dawley rat, and to provide ideal animal model for imaging diagnosis and interventional therapy. Methods One-hundred and forty male SD rats were administrated with 0. 95 g/L DENA for 10 weeks, and MR/ was performed for inspecting pathological changes of rat livers on the following week. When the liver tumor was proved then the rat will be the candidate for sequential procedures, otherwise the animal continued under observation until next MR/ examination after 4 weeks. DSA was done in 64 rats for detecting blood supply of liver tumors. Animals were sacrificed with an overdose of chloral hydrate, The representative tumor tissues were fixed in 10% formalin and 2. 5% glutaraldehyde for light and electron microscopy analysis respectively. Alpha fetoprotein （AFP） and hepatoeyte were assaied by immunohistochemistry technique in order to identify intrinsic trait of the harvested tumors. Results The earliest induced tumor was detected on llth week and the latest was on 20th week by MR/, and the median period was 13.9 weeks. Tumor size ranged from 2 mm to40 mm in diameter. The rate of single and multi-induced tumor was 9. 7% （7/72） and 90. 3% （65/72） , respectively. 87. 7% （57/65） of the induced multiple tumors was with hepatocirrhosis and 18.1% of these tumors combined with extrahepatic neoplasm or metastasis. Plenty blood supply was proved by DSA in most of those tumors. Tumors not only derived from hepatoeyte but also manifested positive expression of AFP. Histological types of these tumors include hepatocellular carcinoma （ HCC ） （92. 0% , 66/72 ） , intrabepatic cholangioeareinoma （ICC） （ 4. 0% , 3/72 ）, and combined HCC and ICC （ 4. 0% , 3/72 ） , respectively. Electro-microscope analysis indicated that cytoplasm and organelle of induced tumors were abnormal distinctly compared with those of non-carcinomatous cells. Conclusion DENA can induce ideal rat liver cancer as a feasible animal model, MRI is the best approach for scrutinizing pathological changes of rat livers during induced period.
出处
《中华放射学杂志》
CAS
CSCD
北大核心
2007年第3期312-316,共5页
Chinese Journal of Radiology
基金
纽约中华医学会基金(CMB No.82-412)
高等学校博士学科点专项科研基金(20030610090)
四川省应用基础研究项目(04JY029-002-14)
四川省中医药管理局科研专项基金(2004B03)
