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一个新的原发性肝细胞癌模型的建立及相关基因表达测定 被引量:7

Establishment of a new primary hepatocellular carcinoma model and its expression of some kinds of associated genes
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摘要 目的 为研究肝细胞癌发生发展的机制建立稳定可靠的动物模型。方法 取32只昆明小鼠,采用四氯化碳(CCl_4)/乙醇诱导20周,观察肝癌发生的情况。另取8只作为正常对照。我们采用Northern blot的方法检测了醛缩酶A的mRNA的表达,采用逆转录-聚合酶链反应(RTPCR)的方法检测了甲胎蛋白(AFP)、Cyclin D1、p53、转化生长因子-β1(TGF-β1)、TGF-β1 Ⅰ型受体(TβRI)、Smad4等与肝硬化、肝癌相关的部分基因的mRNA的表达状况。结果 32只昆明小鼠共死亡15只,最后剩余的17只昆明小鼠全部发生肝癌。而正常对照组8只小鼠,其肝脏均未发现明显异常。诱导组小鼠的肝细胞癌类型以中、高分化为主。醛缩酶A、AFP、Cyclin D1、TGF-β1、TβRI、Smad4在肝硬化、肝癌组织中表达不同程度增强,而p53在肝癌组织中表达有所减弱。结论 应用四氯化碳/乙醇诱发的昆明小鼠肝癌,在经历了肝炎、肝硬化的基础上形成,与人肝癌的发生发展过程非常相似。肝脏基因表达的情况也为肝硬化、肝癌的基因治疗提供了一些理论依据。因此,该模型对人类研究肝癌的发生发展及治疗都有实际应用价值,是较理想的肝癌实验动物模型。 Objective To study the mechanism of occurrence and development of hepatocellular carcinoma (HCC), a stable and credible animal model of HCC was established. Methods Thirty-two Kunming mice were induced for 20 weeks by CCl_4/ethanol. The occurrence and development of HCC were observed. Another 8 of Kunming mice served as normal control group. Aldolase A was detected by Northern Blot. α-fetoprotein (AFP), CyclinD1, p53, transforming growth factorβ1 (TGF-β1), type Ⅰ receptor of transforming growth factor β1 (TβR Ⅰ ) and Smad4 were investigated by reverse transcription-polymerase chain reaction (RT-PCR). Results Of all the 32 Kunming mice induced by carbon tetrachloride (CCl_4)/ethanol, 17 mice were left alive with hepatocellular carcinogenesis, and the remaining 15 died during the inducing period. Eight mice in the normal control group showed no liver abnormality. Most of the induced hepatocellular carcinomas were middifferentiation and high differentiation. The mRNA expression of AFP, CyclinD1, TGF-β1, TβR Ⅰ and Stand4 was increased to varying degrees in the tissues of cirrhosis and liver cancer was compared with normal liver tissue. Conclusion After undergoing hepatitis, liver fibrosis and cirrhosis, the Kunming mice induced by CCl_4/ethanol developed HCC. This course was very similar with that of human HCC. It is believed that this model was an ideal and suitable one for us to study the occurrence and development of human HCC. The information of the gene expression provides some theoretic basis for the gene therapy of HCC. So this animal model of HCC is ideal and practical.
出处 《中华实验外科杂志》 CAS CSCD 北大核心 2004年第8期931-933,i001,共4页 Chinese Journal of Experimental Surgery
关键词 肝癌 肝硬化 TGF-β1 表达 SMAD4 癌发生 发生发展 昆明小鼠 醛缩酶 RNA Carbon tetrachloride Ethanol Kunming mouse Carcinoma, hepatocellular
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