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中药降糖复方水提取物对KK-Ay糖尿病小鼠骨骼肌糖代谢PI3K/Akt信号通路的影响

Effect of water extract from Jiangtang Decoction on PI3K/Akt signal pathway of skeletal muscle metabolism in KK-Ay diabetic mice

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【作者】 洪金妮黎巍威张宁富宏王学美

【Author】 HONG Jin-ni;LI Wei-wei;ZHANG Ning;FU Hong;WANG Xue-mei;Integrated laboratory of Traditional Chinese Medicine and Western Medicine, Peking University First Hospital;

【机构】 北京大学第一医院中西医结合研究室

【摘要】 目的研究中药降糖复方水提取物(WEJTD)对自发性2型糖尿病(T2DM)模型KK-Ay小鼠骨骼肌糖代谢PI3K/Akt信号通路的影响。方法将KK-Ay小鼠按随机数法随机分为5组:模型组、盐酸二甲双胍(MH,250 mg/kg)组和WEJTD低、中、高剂量(2、4、8 g/kg)组,C57BL/6J小鼠作为对照组,每天ig给药1次,共12周,对照组和模型组ig等体积蒸馏水。给药12周后,取小鼠血清,ELISA试剂盒法检测胰岛素水平;Trizol法提取肌肉组织中的RNA,荧光实时定量PCR(q RT-PCR)检测磷脂酰肌醇激酶-3(PI3K)、蛋白激酶B(Akt)、葡萄糖转运蛋白-4(GLUT-4)、糖原合成酶激酶-3β(GSK-3β)、糖原合成酶(GS)、胰岛素受体底物(IRS-1)m RNA水平。结果与模型组比较,WEJTD高、中剂量显著上调小鼠血清胰岛素水平、骨骼肌中IRS-1 m RNA水平(P<0.05、0.001);高、中、低剂量均显著下调骨骼肌中GSK-3βm RNA水平,显著上调PI3K、Akt、GLUT-4、GS m RNA水平(P<0.05、0.01、0.001)。结论中药降糖复方通过上调PI3K/Akt信号通路,减少糖原沉积,刺激骨骼肌中葡萄糖转运。

【Abstract】 Objective To explore the effects of water extract from Jiangtang Decoction(WEJTD) on PI3 K/Akt signal pathway of skeletal muscle metabolism in KK-Ay diabetic mice.Methods Totally 50 KK-Ay mice were randomly divided into five groups: model group, metformin(positive drug, 250 mg/kg) group, WEJTD low, medium, and high dose(2, 4, and 8 g/kg) group, with 10 C57 BL/6 J mice as normal group. The relative drugs were ig administered once a day for 12 weeks, and mice in control group and model group were perfused with distilled water of equal volume. After 12 weeks’ oral administration, mice were executed to separate serum, serum insulin level was detected by ELISA kit method; RNA was extracted from muscle tissue by Trizol, and real-time PCR were used to detect the level of PI3 K, Akt, GLUT-4,GSK-3β,GS and IRS-1 m RNA. Results WEJTD can down-regulate concentration of insulin in serum and GSK-3β m RNA in skeletal muscle(P < 0.05 and 0.001), and down-regulate m RNA of PI3 K, Akt, IRS-1, GLUT-4, and GS in skeletal muscle(P < 0.05, 0.01, and 0.001). Conclusion WEJTD decreased glycogen deposition and stimulated glucose transport in skeletal muscle through upregulation of PI3 K/Akt signaling pathway.

【基金】 国家自然科学基金面上项目(81573763);国家自然科学基金重点项目(81530099);北京市自然科学基金(7172221);国家重点研发计划(2016YFE0116200)
  • 【文献出处】 药物评价研究 ,Drug Evaluation Research , 编辑部邮箱 ,2017年10期
  • 【分类号】R285.5
  • 【被引频次】13
  • 【下载频次】433
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