Page 65 - 《中国药房》2021年第9期

Effects of Mangiferin on Glucose and Lipid Metabolism of Insulin-resistant HepG2 Cells
LI Zilin ，JIN Huijie ，FANG Jia ，LIU Yiming ，LIN Aihua（1. Phase Ⅰ Clinical Trial Center，Guangdong
1
1
1
3
1，2
Provincial Hospital of TCM/the Second Affiliated Hospital of Guangzhou University of TCM，Guangzhou
510120，China；2. Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine
Syndrome，Guangdong Provincial Hospital of TCM/the Second Affiliated Hospital of Guangzhou University of
TCM，Guangzhou 510120，China；3. Dept. of Pharmacy，Guangdong Provincial Hospital of TCM/Zhuhai
Hospital，the Second Affiliated Hospital of Guangzhou University of TCM，Guangdong Zhuhai 519000，China）

ABSTRACT OBJECTIVE：To analyze the effects of mangiferin（MGF）on glucose and lipid metabolism in insulin resistance
（IR）HepG2 cells，and to explore the potential mechanism. METHODS：Using human hepatoma HepG2 cells as research objects，
1 mmol/L palmitic acid and 2 mmol/L oleic acid were used to establish the IR-HepG2 cell model. Using metformin hydrochloride as
positive control，the effects of low-concentration，medium-concentration and high-concentration MGF（125，250，500 μmol/L）on
the corrected glucose consumption，the contents of triglyceride（TG）and total cholesterol（TC）in IR-HepG2 cells were detected.
The mRNA expression of APN，AdipoR2，APPL1，AMPK in the upstream of AMPK signaling pathway and IRS-1，Akt and
GLUT4 in the downstream insulin signaling pathway were detected by RT-PCR. The phosphorylation level of AMPK protein was
detected by Western blot assay. RESULTS：Compared with control group，corrected glucose consumption，mRNA expression of
APN，AdipoR2，APPL1，AMPK，IRS-1 and GLUT4，as well as the phosphorylation level of AMPK protein were decreased
significantly in model group，while the contents of TG and TC were increased significantly（P＜0.05 or P＜0.01）. Compared with
model group， corrected glucose consumption， mRNA expression of APN （except for MGF medium-concentration and
high-concentration groups），AdipoR2，APPL1，AMPK（except for MGF medium-concentration and high-concentration groups），
IRS-1（except for MGF medium-concentration and high-concentration groups），Akt（except for positive control group），GLUT4
（except for MGF high-concentration group）were increased significantly in administration groups，while the contents of TG and TC
were decreased significantly（P＜0.05 or P＜0.01）. CONCLUSIONS：Mangiferin may activate APN，which is the upstream target
of pathway，and then regulate AMPK signaling pathway，so as to promote glucose uptake of IR-HepG2 cells，reduce TG and TC
contents，and improve IR and abnormal glucose and lipid metabolism.
KEYWORDS Mangiferin；Insulin resistance；Human HepG2 cells；Glucose and lipid metabolism；AMPK signaling pathway；
APN

2 型糖尿病（T2DM）多由胰岛素抵抗（IR）和 B 细胞 作用与 AMPK 及其下游胰岛素信号通路 Akt 和 GLUT4
[1]
功能障碍所致 ，其中IR主要表现为肝脏、肌肉、脂肪等 的表达有关 [9－10] 。有研究表明，MGF能提升糖尿病IR模
靶组织对胰岛素的敏感性下降以及对葡萄糖的摄取及 型大鼠血清中APN的含量 ，但其是否能通过激活这一
[11]
[2]
利用减少 。腺苷一磷酸活化蛋白激酶（AMPK）分布于 上游靶点进而调控 AMPK 信号通路中的各关键因子的
各组织中，其活化后能增加机体对胰岛素的敏感性，改 表达，尚有待进一步探讨。基于此，本研究以 HepG2 肝
善 IR 和糖脂代谢紊乱，从而减轻 T2DM 相关症状 。有 脏细胞 IR 模型（即 IR-HepG2 细胞模型）为对象，初步探
[3]
研究指出，脂联素（APN）为 AMPK 信号通路的上游靶 讨了 MGF 对其糖脂代谢以及 AMPK 信号通路的影响，
点，是该信号通路中的关键信号分子，可通过与脂联素受 旨在为 MGF 改善 T2DM 患者 IR 的作用机制研究提供
体2（AdipoR2）结合而激活AMPK，而APPL1是AdipoR2 参考。
与 AMPK 之间的关键衔接蛋白 [4－5] 。当 AMPK 被激活 1 材料
后，AMPK可进一步促进下游胰岛素信号通路中胰岛素 1.1 主要仪器
受体底物1（IRS-1）的磷酸化，激活蛋白激酶B（Akt）；Akt 本研究所用主要仪器包括 3111 型 CO2细胞培养箱
活化可促使细胞中的葡萄糖转运体4（GLUT4）由细胞质 （美国Thermo Fisher Scientific公司）、Synergy H1型多功
转移到细胞膜，从而促进葡萄糖的摄取和利用，最终改 能酶标仪（美国BioTek公司）、HR40-ⅡA2型生物安全柜
[6]
善IR 。 （广州火元医疗器械有限公司）、AB135-S 型电子天平
知母为百合科植物知母 Anemarrhena asphodeloi- （瑞士 Mettler Toledo 公司）、Microfuge 16 型台式微量离
des Bge.的干燥根茎，其主要活性成分之一的芒果苷 心机和 Allegra X-22R 型多功能台式冷冻离心机（美国
（MGF）具有改善 IR 和糖脂代谢紊乱的作用 [7－8] ，且这种 Bechman Coulter 公司）、7500 型荧光定量基因扩增仪和

中国药房 2021年第32卷第9期 China Pharmacy 2021 Vol. 32 No. 9 ·1083 ·