[關鍵詞]
[摘要]
目的 研究中藥降糖復方水提取物(WEJTD)對自發(fā)性2型糖尿?。═2DM)模型KK-Ay小鼠骨骼肌糖代謝PI3K/Akt信號通路的影響。方法 將KK-Ay小鼠按隨機數(shù)法隨機分為5組:模型組、鹽酸二甲雙胍(MH,250 mg/kg)組和WEJTD低、中、高劑量(2、4、8 g/kg)組,C57BL/6J小鼠作為對照組,每天ig給藥1次,共12周,對照組和模型組ig等體積蒸餾水。給藥12周后,取小鼠血清,ELISA試劑盒法檢測胰島素水平;Trizol法提取肌肉組織中的RNA,熒光實時定量PCR(qRT-PCR)檢測磷脂酰肌醇激酶-3(PI3K)、蛋白激酶B(Akt)、葡萄糖轉運蛋白-4(GLUT-4)、糖原合成酶激酶-3β(GSK-3β)、糖原合成酶(GS)、胰島素受體底物(IRS-1)mRNA水平。結果 與模型組比較,WEJTD高、中劑量顯著上調小鼠血清胰島素水平、骨骼肌中IRS-1 mRNA水平(P<0.05、0.001);高、中、低劑量均顯著下調骨骼肌中GSK-3β mRNA水平,顯著上調PI3K、Akt、GLUT-4、GS mRNA水平(P<0.05、0.01、0.001)。結論 中藥降糖復方通過上調PI3K/Akt信號通路,減少糖原沉積,刺激骨骼肌中葡萄糖轉運。
[Key word]
[Abstract]
Objective To explore the effects of water extract from Jiangtang Decoction (WEJTD) on PI3K/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 C57BL/6J 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 PI3K, Akt, GLUT-4,GSK-3β,GS and IRS-1 mRNA. Results WEJTD can down-regulate concentration of insulin in serum and GSK-3β mRNA in skeletal muscle (P<0.05 and 0.001), and down-regulate mRNA of PI3K, 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 PI3K/Akt signaling pathway.
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[基金項目]
國家自然科學基金面上項目(81573763);國家自然科學基金重點項目(81530099);北京市自然科學基金(7172221);國家重點研發(fā)計劃(2016YFE0116200)