c-jun氨基末端激酶在非酒精性脂肪肝病胰岛素抵抗大鼠中的表达及意义

Expression and significance of c-Jun N-terminal kinase (JNK) in the rat of nonalcoholic fatty liver disease with insulin resistance

目的观察c-jun氨基末端激酶(JNK)在非酒精性脂肪肝病(NAFLD)大鼠中的表达及在胰岛素抵抗(IR)发生中的意义。方法雄性SD大鼠32只,随机分为8周对照组、12周对照组、8周模型组和12周模型组各8只,分别给予正常饮食或高脂饮食喂养8周和12周。于第8周和第12周用生化法检测大鼠血清甘油三酯(TG)、空腹血糖(BS)含量;正糖高胰岛素钳夹实验检测IR水平;免疫组织化学和Western blot技术检测肝组织中JNK表达变化。结果大鼠NAFLDIR模型组TG、BS含量较对照组增高,随着喂养时间的延长,大鼠肝细胞脂肪变性及IR水平逐渐加重,JNK阳性细胞和JNK蛋白表达强度逐渐增加,JNK的表达强度与IR呈正相关。差异均有显著性(P<0.05)。结论高脂饮食喂养8周能够成功构建NAFLDIR大鼠模型,肝细胞JNK可能参与了NAFLDIR的发生和发展。

[Objectives] To investigate the expression of c-Jun N-terminal kinase （JNK） in the nonalcoholic fatty liver disease of rats, and study the significance of JNK in insulin resistance occurring. [Methods] Thirty-two male SD rats were randomly divided into four groups： control group beer, fed 8 weeks, control group been fed 12 weeks, high-fat diet group been fed 8 weeks, and high-fat diet group been fed 12 weeks. Each group had been given norreal diet or high-fat diet for 8 or 12 weeks separately. In the 8 th week and the 12 th week, the level of serum triglyceride （TG）, blood sugar （BS） were measured by biochemical method. The level of insulin was detected by euglycemic hyperinsttlinemic clamp technique. The expression of JNK in the hepatocytes was detected by immunohisto-chemistry and Western blot. [Results] Compared with the control group, TG and BS levels of NAFLD IR group were higher;, hepatocytes fatty degeneration and level of insulin resistance aggravated through extension of feeding time; the expression of JNK and the number of JNK positive cell gradually increased. A positive correlation was found between the expression intensity of JNK and IR. There were significant differences between two groups （P〈0.05）. [Conclusions] NAFLD IR rat models could be estabhshed successfully by feeding high-fat diet within 8 weeks. And hepatocyte JNK participated in the progression of rat NAFLD.