【作者】 李有贵； 钟石； 朱俭勋； 胡桂燕； 计东风；

【Author】 LI You-gui;ZHONG Shi;ZHU Jian-xun;Gui-Yan Hu;JI Dong-feng;Sericultural Research Institute,Zhejiang Academy of Agricultural Sciences;

【机构】 浙江省农业科学院蚕桑研究所；

【摘要】 目的:探讨桑叶1-脱氧野尻霉素（DNJ）对高脂饲料诱导小鼠糖脂代谢调控作用机制。方法:高脂饲料诱导高脂血症性模型小鼠,给予DNJ(50mg·kg^-1)处理90天后,测定小鼠血糖、血脂、胰岛素、葡萄糖激酶（GK）、己糖激酶（HK）、丙酮酸激酶（PK）、载脂蛋白（APO-A1、APO-B100）等生化指标水平变化,RT-PCR、Western蛋白质印迹法检测肝脏内脂蛋白脂酶（LPL）、GK、葡萄糖激酶调节蛋白（GKRP）、PK、丙酮酸羧化酶（PCB）、APO-A1、APO-B100、甘油激酶（Gly-K）、3-磷酸甘油脱氢酶（G3PD）、内质网脂酰辅酶A合成酶（Acyl-coA-S）等表达水平变化,结合石蜡切片观察肝脏病理变化。结果:桑叶DNJ可降低高脂饲料诱导的模型小鼠餐后血糖、总胆固醇（TG）、胰岛素水平以及胰岛素抵抗指数;提高肝脏GK、PK活性及APO-A1、APO-B100含量,提高糖脂转运代谢关键蛋白GK、GKR、PK、APO-A1、APO-B100、LPL、AcylCoA-S、Gly-K、G3PD等表达,降低糖异生关键酶PCB、PEPCK的蛋白水平;高脂饲料导致小鼠肝索排列紊乱,遍布脂滴,DNJ处理后小鼠肝脏脂滴数量明显减少。结论:桑叶DNJ可通过调节葡萄糖、甘油三酯代谢关键酶的表达,加速血糖、血脂的转运代谢,从而降低高脂诱导的脂肪肝损伤。更多还原

【Abstract】 Objective:To provide insights into the regulation mechanism of glucose and lipid metabolism by DNJ from mulberry leaves on high-fat diet induced mice.Methods:Hyperlipidemia model mice were induced by high-fat diet,then treated with DNJ(50 mg·kg^-1)for 90 days.Serum glucose,lipids,insulin,glucokinase（GK）,hexokinase（HK）.pyruvate kinase（PK）,apolipoprotein（APO-A1,APO-B100）and other physiological index were measured.RT-PCR and Western blot were carried out to observe the expression of Lipoprotein lipase（LPL）,GK,glucokinase regulatory protein（GKRP）,PK,pyruvate carboxylase（PCB）,APO-A1,APO-B100,glycerol kinase（Gly-K）,3-phosphate dehydrogenase（G3 PD）.endoplasmic reticulum acyl coenzyme A synthetase（Acyl-coA-S）in liver.Moreover,histopathological examinations of liver were also observed with HE staining.Results:Postprandial blood glucose,total cholesterol（TG）.insulin level and insulin resistance index were significantly decreased in DNJ treated group compared to high-fat diet induced model group.Meanwhile,the activities of GK,PK and the content of APO-A1,APO-B100 were evidently increased,the expressions of GK,GKRP.PK,APO-A1,APO-B100,LPL,Acyl-CoA-S,Gly-K and G3 PD were also remarkably up-regulated,but the gluconeogenesis enzymes PCB,PEPCK were significantly down-regulated in DNJ treated mice compared to model control.Hepatic histopathological analysis revealed that hepatic cord degeneration and the lipid droplets were markedly increased in high-fat diet induced mice,DNJ(50 mg·kg^-1) treatment significantly restored these abnormalities.Conclusion:These results suggest that DNJ could decrease blood glucose and lipid level in high-fat diet induced fatty liver mice via regulating the expression of enzymes involved in glucose and lipid metabolism,thereby reducing fatty liver injury induced by high-fat diet.更多还原