中文摘要：

目的通过尾静脉高压注射含有AKT/SB基因质粒的方法,构建一种新型的小鼠非酒精性脂肪肝模型。方法将40只雌性FVB/N小鼠随机分为正常组（n=15）,模型组（n=15）,对照组（n=5）,治疗组（n=5）。正常组与模型组分别给予尾静脉高压注射生理盐水和AKT/SB质粒,于第1、2、3周分批处死,每批处理5只。对照组与治疗组给予尾静脉高压注射AKT/SB质粒,第3周治疗组开始予以白藜芦醇灌胃（0.04g/kg）,对照组予以等量0.5%CMC-Na溶液灌胃,第5周处死全部对照组和治疗组小鼠。检测小鼠体重,肝湿重,肝指数,血清ALT、AST、TG、TC水平及肝组织中脂肪合成相关蛋白的表达水平,肝脏组织切片进行病理学观察,用以评价不同组别小鼠的病理生理变化。结果模型组小鼠2周后就出现肝功能损伤,脂质代谢紊乱,肝脏脂肪变性明显增加,并出现纤维化和明显的炎性浸润,且造模时间越长,病变程度越严重。治疗组小鼠和对照组小鼠相比,血清中ALT、AST、TC水平均有不同程度的下降,肝组织中脂肪合成相关蛋白的表达水平有所下降,且肝脏切片染色观察脂肪形成明显减少。结论通过尾静脉高压注射方法在肝脏表达AKT基因,FVB/N小鼠在3周内可形成病变程度逐步加重的非酒精性脂肪肝模型。

英文摘要：

Objective To establish a novel non-alcoholic fatty liver animal model by hydrodynamic injections of plasmids containing AKT/SB gene via the tail vein. Methods Forty FVB/N female mice were randomly divided into normal group（n= 15）,model group（n=15）,control group（n 5）and treatment group（n=5）. Animals in normal group and model group were treated by hydrodynamic injections of normal saline and naked AKT/SB plasmids, respectively, via the tail vein. Every five mice in the two groups were killed at the lst,2nd,3rd week,respectively. Mice in treatment group and control group were treated by hydrodynamic injections of naked AKT/SB plasmids through the tail vein and then treated with resveratrol（i, g 0.04 g/kg）and equal 0.5% CMC-Na solution,respectively,at the 3rd week. They were sacrificed in both control and treatment groups at the 5th week. The body weight,liver weight,serum ALT, AST,TC and TG levels and expression levels of protein related to lipid synthesis were measured. Liver tissues were obtained and histopathologically examined to evaluate the physiologic and patholog- ical changes in different groups. Results At 2 weeks,the liver function injury was found in mice in model group, the disorder of lipid metabolism occurred,and the hepatic steatosis was significantly increased. Besides, there were obvious inflammatory in- filtration and fibrosis in model group. The lesions became severe with the time of modeling. The serum levels of ALT, AST and TG and adipogenesis-related protein levels were significantly decreased and the adipogenesis was markedly reduced in liver tis- sues in treatment group when compared with those in model group. Conclusion Non alcoholic fatty liver disease models in FVB/N mice were successfully established by hydrodynamic injections of AKT/SB gene via the tail vein,and the lesions tended to gradually worsen within 3 weeks.