CAJ | 학술논문

目的：胰岛素抵抗是2型糖尿病的重要特征及防治难点，其机制尚未明确。本文主要研究在高脂饮食诱发的胰岛素抵抗过程中，氧化应激水平及核-线粒体轴的分子改变及可能机制。方法：以雄性C57小鼠为实验对象，随机分为2组，对照组采用正常饮食饲喂，高脂组采用含10%猪油高脂饮食饲喂以诱导胰岛素抵抗模型。检测肝脏组织活性氧、脂质过氧化物丙二醛(MDA)及脂质累积水平，测定肝组织中P-Akt、Nrf2、核呼吸因子1(NRF-1)和线粒体转录因子A(mtTFA)的蛋白表达量。结果：与对照组相比，长期使用高脂饲料喂饲动物可导致动物糖耐量及胰岛素耐量下降，使肝组织内脂质累积水平和活性氧水平显著增加，丙二醛含量增加约30%，胰岛素信号分子P-Akt 蛋白表达下降约45%，Nrf2、NRF-1和mtTFA蛋白表达下降20%~30%。结论：在高脂饮食诱发胰岛素抵抗过程中，氧化应激与Nrf2/NRF-1/mtTFA分子通路的功能障碍可能发挥了重要作用。
목적：이도소저항시2형당뇨병적중요특정급방치난점，기궤제상미명학。본문주요연구재고지음식유발적이도소저항과정중，양화응격수평급핵-선립체축적분자개변급가능궤제。방법：이웅성C57소서위실험대상，수궤분위2조，대조조채용정상음식사위，고지조채용함10%저유고지음식사위이유도이도소저항모형。검측간장조직활성양、지질과양화물병이철(MDA)급지질루적수평，측정간조직중P-Akt、Nrf2、핵호흡인자1(NRF-1)화선립체전록인자A(mtTFA)적단백표체량。결과：여대조조상비，장기사용고지사료위사동물가도치동물당내량급이도소내량하강，사간조직내지질루적수평화활성양수평현저증가，병이철함량증가약30%，이도소신호분자P-Akt 단백표체하강약45%，Nrf2、NRF-1화mtTFA단백표체하강20%~30%。결론：재고지음식유발이도소저항과정중，양화응격여Nrf2/NRF-1/mtTFA분자통로적공능장애가능발휘료중요작용。
OBJECTIVE:Insulin resistance (IR) is a major characteristic of type 2 diabetes millitus which is difficult to be prevented and treated,and its pathogenesis is still uncertain. The aim of this study was to investigate the change of oxidative stress and nuclear-mitochondria axis in hepatic tissue during the process of insulin resistance induced by high-fat-diet in mice. METHODS:Male C57 mice were randomly divided into 2 groups,the mice in control group were fed with normal chow while those in high fat diet group were fed with 10% lard oil containing diet to induce insulin resistance. The hepatic reactive oxygen species level,malondialdehyde (MDA) content and lipid accumulation were tested. P-Akt,Nrf2,NRF-1 and mtTFA expression in liver tissue were determined by Western blot.RESULTS:Compared with controls,mice fed with a high fat diet could induce insulin resistance. During this process,hepatic fat and ROS accumulation were both increased,the MDA content was also elevated by about 30%. The expression of insulin signal transduction protein P-Akt was attenuated by 45% whilst the expressions of Nrf2,NRF-1 and mtTFA were decreased by 20%-30%.CONCLUSION:Oxidative stress and dysfunction of Nrf2/NRF-1/mtTFA axis may play important roles in the development of insulin resistance induced by a high fat diet.