人肝癌NOD-SCID小鼠原位移植模型的建立及其生物学特性的研究

Establishment of an orthotopic transplantation model of human hepatocellular carcinoma in NOD-SCID mice and its biological characteristics

目的：建立人肝癌NOD-SCID小鼠原位移植模型,并通过和裸小鼠原位移植模型生物学特性的比较,对两种不同类型免疫缺陷动物在人肝癌异种移植方面的应用价值进行初步探讨。方法：将组织学完整的SMMC-LTNM瘤块植入NOD- SCID小鼠和裸小鼠肝脏内,观察成瘤率、肿瘤体积和重量、脏器的转移情况以及血清甲胎蛋白(AFP)、γ-谷氨酰转肽酶同工酶Ⅱ(γ-GTⅡ)等。结果：NOD-SCID小鼠于移植后5周可扪及肿瘤的生长,成瘤率为100%,11周肿瘤体积为(4．48±0．93) cm^3,瘤重为(7．02±1．15)g,肺部转移率为53．85%；裸小鼠于移植后6～7周可扪及肿瘤的生长,成瘤率为100%,11周肿瘤体积为(1．02±0．70)cm^3,瘤重为(2．87±0．44)g,体内未见转移发生。NOD-SCID小鼠的瘤体积、瘤重、肺转移率均高于裸小鼠(P＜0．01)。两者均保持AFP高分泌和γ-GTⅡ同工酶阳性的特性。结论：建立了一个与临床相似的人肝癌动物模型,与裸小鼠相比,NOD-SCID小鼠在建立人肝癌异种移植模型方面有更大的应用价值。

Objective： To establish an orthotopic transplantation model of human hepatocellular carcinoma in NOD-SCID mice and compared with the biological characteristics of nude mice to discuss the application value of the two immunodeficiency animals in xenograft transplantation of human hepatocellular carcinoma. Methods： Histologically intact SMMC-LTNM tumor tissues we transplanted into the livers of NOD-SCID and nude mice. The occurrence rate, volume, weight, and metastasis of tumor were observed. The level of alpha-fetoprotein （AFP） and gamma-glutamyhransferase Ⅱ （γ-GT Ⅱ） were measured. Results：The growth of tumor in NOD-SCID mice was palpated by human touch at the 5th week after transplantation. The tumor occurrence rate was 100%. The volume, weight, and lung metastasis rate of the tumor was （4.48±0. 93） cm^3, （7.02± 1. 15） g, and 53.85 % at the 11th week, respectively. The growth rate of the tumor was 100 % in nude mice. The tumor was palpated by human touch between the 6th and the 7th week in nude mice. The tumor occurrence rate was 100%. The tumor had the volume of （1.02±0.70） cm3 and weighed （2.87±0.44） g at the 11th week after transplantation. No metastasis was observed in vivo. The volume, weight, and metastasis rate of the tumor in NOD-SCID mice were all significantly higher than those in nude mice （P〈0.01）. The two breeds of animals all kept the characteristics of higher AFP levels and positive γ-GT Ⅱ. Conclusion. We established an animal model that simulates the clinical features of human hepatocellular carcinoma. Compared with nude mice NOD- SCID mice had greater application value in establishment of xenograft transplantation model of human hepatocellular carcinoma.