AKT通过调控FASN的脂质代谢促进小鼠肝脏肿瘤的形成  

AKT Promotes Tumorigenesis in Mice Through Regulation FASN Lipid Metabolism

作　　者：喻兆阳 薛慧颖 YU Zhao-yang;XUE Hui-ying(Department of Pharmacy,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;School of Pharmacy,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院药学部,湖北武汉430030 [2]华中科技大学同济医学院药学院,湖北武汉430030

出　　处：《福建师范大学学报（自然科学版）》2019年第3期52-58,共7页Journal of Fujian Normal University：Natural Science Edition

基　　金：国家自然科学基金资助项目(81201553);华中科技大学自主创新研究基金(514/5003514011)

摘　　要：使用尾静脉高压注射基因转染技术将不同质量AKT基因转染至FVB/N小鼠肝脏,探讨不同AKT表达量对AKT/Ras介导的小鼠肝癌发生发展的影响.随机将6周龄雌性FVB/N小鼠分为3组,对照组尾静脉高压注射空载体质粒,模型组A尾静脉高压注射75μg AKT、75μg Ras质粒,模型组B尾静脉高压注射150μg AKT质粒、75μg Ras质粒.并在小鼠造模后第2、4、6周处死小鼠,记录体质量并取肝脏组织称肝质量,检测血清ALT、AST水平,观察并记录肝癌生长情况.最后检测小鼠肝脏AKT、p-AKT、FASN和Ras的表达情况,并检测3组小鼠肝脏脂肪累积变化情况.结果显示,在2周时模型组A与模型组B小鼠血清中ALT和AST水平均呈不同程度的升高,提示有肝功能损伤,但两组间无显著差异.两模型组小鼠肝脏均形成肿瘤,但模型组A小鼠体质量、肝脏质量、肿瘤结节数量和大小明显低于模型组B小鼠.AKT基因可明显增加小鼠肝脏组织FASN的表达,并提高小鼠肝脏组织脂质累积量,促进小鼠肝癌的发生和发展.Different quantity of AKT gene were transfected into the liver of FVB/N mice by hydrodynamic transfection technique to investigate the effect of different AKT expression levels on AKT/Ras-mediated hepatocarcinogenesis in mice.6-week-old female FVB/N mice were randomly divided into 3 groups.The control group was injected with empty vector plasmid.Mice in model group A were injected with 75 μg AKT and 75 μg Ras plasmid.Mice in model group B were injected with 150 μg AKT plasmid and 75 μg Ras plasmid.After injection,the mice were sacrificed at the 2 nd week,4 th week,and 6 th for further study.Meanwhile,the body and liver weight were recorded,and ALT and AST levels were measured.Finally,the expression of AKT,p-AKT,FASN and Ras and the changes of liver fat accumulation in the three groups were detected.The results showed that at 2 weeks,the serum levels of ALT and AST in model group A and B increased to different degrees,suggesting liver function damage.However,there was no significant difference between the two groups.Tumors were formed in both of the two model groups,but in model group A,the body weight,liver weight,size and number of tumor nodules were significantly lower than those in model group B.AKT gene can significantly increase the expression of FASN and lipid accumulation of liver tissue in mice,and it can promote the occurrence and development of liver cancer.

关 键 词：肝细胞癌 高压注射转染技术 AKT基因 RAS基因 脂质累积 

分 类 号：R735.7[医药卫生—肿瘤]