熊果酸通过PPARα/γ改善HepG2细胞胰岛素抵抗模型糖代谢的机制  

The mechanism of ursolic acid in ameliorating insulin resistance HepG2 cell glycometabolism via PPARα/γ

作　　者：王冠梁[1] 刘甲寒[1] 李迪[1] 王琳[1] 朱德增[1] 

机构地区：[1]第二军医大学附属上海长海医院中医科,200433

出　　处：《中药药理与临床》2012年第4期24-29,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金资助项目(NO:81073116)

摘　　要：目的:观察熊果酸对HepG2细胞胰岛素抵抗模型糖代谢的影响并探讨其机制。方法:通过高浓度葡萄糖诱导HepG2细胞建立胰岛素抵抗模型,采用葡萄糖氧化酶法,氚标记-葡萄糖法和硫酸蒽酮比色法检测熊果酸对HepG2细胞胰岛素抵抗模型的葡萄糖消耗、摄取和糖原合成量的影响;采用Real time-PCR和Western blot法检测熊果酸对HepG2细胞胰岛素抵抗模型PPARα、PPARγ、PEPCK的mRNA转录水平以及蛋白表达的影响。结果:12.5μmol/L和25μmol/L熊果酸处理HepG2细胞胰岛素抵抗模型后,其葡萄糖消耗量、摄取量和糖原合成量明显高于模型对照组。与正常对照组相比,熊果酸可降低HepG2细胞胰岛素抵抗模型PEPCK的mRNA转录水平和蛋白表达量,提高PPARα的mRNA转录水平和蛋白表达量。结论:熊果酸可改善HepG2细胞胰岛素抵抗模型的糖代谢,其作用机制可能是通过激动PPARα/γ、抑制PEPCK的表达来实现。Objective： To explore the effects and mechanism of ursolie acid improving hepatic insulin resistance in HepG2 cell IR model. Meth- ods： We obtained the HepG2 cell IR model by means of high concentration glucose, applying glucose consumption and intake experiment to detect HepG2 information of IR model. We evaluated the effect of UA to the cell viability by the MTT and using the glucose oxidation en- zyme method, 3 H-glucose method, sulfuric anthrone colorimetric method to tested the effect of UA to the glucose consumption/intake and gly-cogen synthesis on the cell IR model. We adopting RT-PCR method to detect mRAN expression of PPARα, PPAR,/, PEPCK genes as well as the Westen-blot method to detect the expression of PPARα, PPARγ, PEPCK protein. Results： 12.5V.mol / L and 25μmol/L UA act on HepG2 ceils IR model for 24 hours, the glucose consumption/intake, glycogen synthesis were significantly higher than model group （ P 〈 0. 01）. Compared with the control group, HepG2 cell IR modrel PPARα protein expression and mRNA decreased significantly （ P 〈 0.01 ）, RRARγ protein expression decreased （ P 〈 0.05 ） , PEPCK protein expression and mRNA increased （ P 〈 0.01 ） ; ursolic acid can reduce PEPCK protein expression and mRNA （P 〈 0.01 ）, increased PPARα protein expression and mRNA （P 〈 0.01 ）. Conclusion： UA can im- prove the glucose metabolism of HepG2 ceil IR model. The mechanism of UA in improving the glucose metabolism of HepG2 cell IR model may be relevant with raising PPARα/γ and inhibition PEPCK expression.

关 键 词：熊果酸 HEPG2细胞 胰岛素抵抗 糖代谢 PPARΑ PPARγ PEPCK 

分 类 号：R285[医药卫生—中药学]