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桑叶1-脱氧野尻霉素对高脂血症小鼠糖脂代谢的影响

Effect of Deoxynojirimycin from mulberry leaves on glucose and lipid metabolism in hyperlipidemia model mice

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【作者】 李有贵钟石朱俭勋孙雨晴胡桂燕计东风

【Author】 Li Yougui;Zhong Shi;Zhu Jianxun;Gui Yanhu;Ji Dongfeng;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】 为了开发利用桑树来源多羟基哌啶生物碱1-脱氧野尻霉素(DNJ)的生物活性功能,研究桑叶DNJ对高脂饲料诱导高脂血症模型小鼠糖脂代谢的影响及调控作用机制。将桑叶DNJ按照50 mg/(kg﹒d)的剂量给予高脂血症模型小鼠90 d后,小鼠餐后血糖、总胆固醇(TG)、胰岛素的浓度以及胰岛素抵抗指数降低(P<0.01),肝脏组织中的葡萄糖激酶(GK)、丙酮酸激酶(PK)活性及载脂蛋白(APO-A1、APO-B100)的含量提高(P<0.01);qRT-PCR检测小鼠肝脏组织中糖脂转运代谢关键蛋白GK、葡萄糖激酶调节蛋白(GKRP)、PK、APO-A1、APO-B100、脂蛋白脂酶(LPL)、内质网脂酰辅酶A合成酶(Acyl-coA-S)、甘油激酶(Gly-K)、3-磷酸甘油脱氢酶(G3PD)等的编码基因转录水平上调(P<0.01),而糖异生关键酶丙酮酸羧化酶(PCB)、磷酸烯醇式丙酮酸羧化激酶(PEPCK)蛋白的表达水平下调。对小鼠肝脏组织的病理切片观察发现,高脂血症模型小鼠的肝细胞索排列紊乱,遍布脂滴,给予桑叶DNJ治疗后,小鼠肝脏细胞的脂滴数量明显减少。研究结果提示,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,从而降低小鼠因高脂饲料诱导造成的肝脏组织损伤。

【Abstract】 In order to develop and utilize the biologically active of 1-DNJ from mulberry leaves,the effect and its underlying mechanism of DNJ on glucose and lipid metabolism were observed in hyperlipidemia model mice.The results showed that the postprandial blood glucose,total cholesterol(TG),insulin level and insulin resistance index were significantly decreased(P<0.01) in DNJ(50 mg/kg﹒d) treated group for 90 days compared to model group.Meanwhile,the activities of glucokinase(GK),pyruvate kinase(PK) and the content of apolipoprotein(APO-A1,APO-B100) were evidently increased(P<0.01).q RT-PCR results showed that the expressions of GK,glucokinase regulatory protein(GKRP),PK,APO-A1,APO-B100,Lipoprotein lipase(LPL),endoplasmic reticulum acyl coenzyme A synthetase(Acyl-coA-S),glycerol kinase(Gly-K) and 3-phosphate dehydrogenase(G3 PD) were also remarkably up-regulated,but the gluconeogenesis enzymes pyruvate carboxylase(PCB),Phosphoenolpyruvate Carboxykinase(PEPCK) were significantly down-regulated(P<0.01) in DNJ treated micecompared to model control.Hepatic histopathological analysis revealed that hepatic cord degeneration and the lipid droplets were markedly increased in hyperlipidemia model mice,DNJ(50 mg/kg﹒d)treatment significantly restored these abnormalities.These results suggest that DNJ could decrease blood glucose and lipid level in hyperlipidemia model mice via regulating the expression of enzymes involved in glucose and lipid metabolism,thereby reducing liver injury induced by high-fat diet.

【基金】 国家自然科学基金项目(No.81403155);现代农产业技术体系专项(No.CARS-22-ZJ0105);浙江省重点研发计划(No.2017C02004)
  • 【会议录名称】 全国桑树产业发展学术研讨会论文集
  • 【会议名称】全国桑树产业发展学术研讨会
  • 【会议时间】2017-08-21
  • 【会议地点】中国湖北武汉
  • 【分类号】R285.5
  • 【主办单位】中国蚕学会、国家蚕桑产业技术体系
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