解耦联蛋白-2基因敲除减轻高脂饮食诱导小鼠脂肪肝缺血再灌注损伤  

UCP-2 gene knock-out alleviates ischemia/reperfusion-induced injury of high fat diet induced fatty liver

作　　者：程锐[1] 王帅[1] 刘涛[1] 王春友[1] 万赤丹[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院普外科,武汉430022

出　　处：《中华实验外科杂志》2010年第2期192-194,共3页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目（30571764）

摘　　要：目的 观察解耦联蛋白-2（UCP-2）基因在脂肪肝缺血再灌注损伤中的作用,探讨以UCP-2为靶点的脂肪供肝预处理新途径.方法 实验动物分为3组：实验组（A组）：UCP-2基因敲除小鼠,给予高脂饮食（n=20）;空白对照组（B组）：野生型同系小鼠,给予正常饮食（n=20）;阴性对照组（C组）：野生型同系小鼠,给予高脂饮食（n=20）.喂养6个月,建屯小鼠脂肪肝模型.各组小鼠阻断门静脉缺血15 min,再灌注24 h后处死,检测肝组织中UCP-2基因表达及三磷酸腺苷（ATP）、活性氧族（ROS）、乳酸脱氢酶（LDH）水平;并行血清丙氨酸转氨酶（ALT）、天门冬氨酸转氨酶（AST）检测及肝组织病理学检测.结果 高脂饮食喂养6个月后成功建立小鼠脂肪肝模型;Western blot证实A组小鼠UCP-2无表达,C组表达明显高于B组;A组ALT、AST、ATP、ROS、LDH的定量值为：（55.33±5.51）、（128.33±7.02）U/L、（28.00±2.00）nmol/L、（165.33±7.09）、（1176.00±22.27）U/pmt;B组上述指标为（25.00±4.58）、（85.33±4.51）U/L、（24.33±4.16）nmol/L、（147.33±7.51）、（707.33±31.64）U/prot;C组为（142.67±13.01）、（220.67±7.02）U/L、（8.67±1.53）nmol/L、（65.00±5.00）、（1748.33±42.52）U/prot,A组和C组差异有统计学意义（P〈0.05）;病理检测表明A组损伤轻于C组.结论 抑制解耦联蛋白-2基因表达能在减轻小鼠脂肪肝急性损伤.Objective To investigate the role of uncoupling protein-2 （UCP-2） in ischemia-reperfusion-（P〈0.05） induced injury and explore a new target for fatty donor hver pretreatment. Methods The animals were divided into 3 groups： experimental group （group A） ： UCP2 gene knock-down mice, feeding on high-fat diet; blank control group （group B） ： homologous series wild type mice, feeding on normal diet; na-gative control group （group C） ： homologous series wild type mice, feeding on high-fat diet. Six months later, the mice in every group were sacrificed. The levels of adenosine-triphosphate （ATP）, reactive oxygen species （ROS）, lactate dehydrogenase （LDH） in hver tissues, and alanine tronsaminase （ALT）, and asparate amin-otransferase （AST） in serum were determed. The pathologic changes were also examined. Results After feed-ing on high fat diet for 6 mouths, the model of fatty liver in mice was established. Western blotting con-firmed that the expression of UCP-2 mRNA was inhibited completely, and the expression level in group C was higher than in group B. The ALT, AST, ATP, ROS and LDH levels in group A were （55.33± 5.51）, （128.33±7.02） U/L, （28.00±2.00） nmol/L, （165.33±7.09）, （1176.00±22.27） U/prot, those in group B were （25.00±4.58）, （85.33±4.51） U/L, （24.33±4.16） nmol/L, （147.33± 7.51）, and （707.33±31.64） U/prot, and those in group C were （142.67±13.01）, （220.67±7.02） U/L, （8.67±1.53 ） nmol/L, （65.00±5.00）, （1748.33±42.52） U/prot, respectively. There was significant difference between group A and group C. Pathologic examination revealed that in group A, the ischemia-reperfusion-induced injury was milder than in group C. Conclusion Inhibiting the expression of UCP-2 attenuates the I/R injury of mouse fatty liver.

关 键 词：脂肪肝 解耦联蛋白-2 缺血 再灌注损伤 

分 类 号：R575.5[医药卫生—消化系统]