加味苓桂术甘汤通过PI3K-Akt/mTOR-S6K1/AMPK-PGC-1信号通路改善肥胖2型糖尿病大鼠糖脂代谢及炎症反应

Jia-pan SUN; Lin SHI; Fang WANG; Jian QIN; Bin KE

doi:10.1007/s11655-020-3285-2

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加味苓桂术甘汤通过PI3K-Akt/mTOR-S6K1/AMPK-PGC-1信号通路改善肥胖2型糖尿病大鼠糖脂代谢及炎症反应

Original Article | Updated：2022-03-18

- 加味苓桂术甘汤通过PI3K-Akt/mTOR-S6K1/AMPK-PGC-1信号通路改善肥胖2型糖尿病大鼠糖脂代谢及炎症反应
- Modified Linggui Zhugan Decoction Ameliorates Glycolipid Metabolism and Inflammation via PI3K-Akt/mTOR-S6K1/AMPK-PGC-1α Signaling Pathways in Obese Type 2 Diabetic Rats
- Chinese Journal of Integrative Medicine 2022年28卷第1期页码：52-59
- Affiliations：
  
  1.Department of Traditional Chinese Medicine, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou (510080),China
  2.Department of Traditional Chinese Medicine,Zhujiang Hospital of Southern Medical University, Guangzhou(510280), China
  3.Department of Oncology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou (510080), China
  4.Department of Traditional Chinese Medicine, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen (518107),Guangdong Province, China
  5.Department of VIP Ward, Sun Yat-sen University Cancer Center, Guangzhou (510060), China
- Author bio：
  
  Prof. KE Bin, E-mail: jackhorn@163.com
- Funds：
  
  the National Natural Science Foundation of China(81302877);Science and Technology Project of Guangdong Province of China(2014A020212056)
- DOI：10.1007/s11655-020-3285-2
  中图分类号：
- 纸质出版日期：2022-01-01，
  
  网络出版日期：2020-11-19，
  
  录用日期：2020-09-21
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Jia-pan SUN, Lin SHI, Fang WANG, 等. 加味苓桂术甘汤通过PI3K-Akt/mTOR-S6K1/AMPK-PGC-1信号通路改善肥胖2型糖尿病大鼠糖脂代谢及炎症反应[J]. Chinese Journal of Integrative Medicine, 2022,28(1):52-59.

Jia-pan SUN, Lin SHI, Fang WANG, et al. Modified Linggui Zhugan Decoction Ameliorates Glycolipid Metabolism and Inflammation via PI3K-Akt/mTOR-S6K1/AMPK-PGC-1α Signaling Pathways in Obese Type 2 Diabetic Rats[J]. Chinese Journal of Integrative Medicine, 2022,28(1):52-59.
Jia-pan SUN, Lin SHI, Fang WANG, 等. 加味苓桂术甘汤通过PI3K-Akt/mTOR-S6K1/AMPK-PGC-1信号通路改善肥胖2型糖尿病大鼠糖脂代谢及炎症反应[J]. Chinese Journal of Integrative Medicine, 2022,28(1):52-59. DOI： 10.1007/s11655-020-3285-2.

Jia-pan SUN, Lin SHI, Fang WANG, et al. Modified Linggui Zhugan Decoction Ameliorates Glycolipid Metabolism and Inflammation via PI3K-Akt/mTOR-S6K1/AMPK-PGC-1α Signaling Pathways in Obese Type 2 Diabetic Rats[J]. Chinese Journal of Integrative Medicine, 2022,28(1):52-59. DOI： 10.1007/s11655-020-3285-2.

摘要

目的:

探讨加味苓桂术甘汤(MLZD)对肥胖2型糖尿病大鼠的保护作用.

方法:

将50只Sprague-Dawley大鼠按随机数字表法分为正常组、肥胖2型糖尿病 (ob -T2DM)组、MLZD低剂量[MLDZ-L

4.625 g/(kg•d)]、MLZD中剂量[MLD-M

9.25 g/(kg•d)及MLZD高剂量[MLD-H

18.5 g/(kg•d)]组

每组10只大鼠. 干预4周后

收集大鼠血液样本及肝脏、胰腺、肌肉组织评估胰岛素抵抗、血脂、脂肪因子和炎症细胞因子水平. 此外

进一步研究磷脂酰肌醇3激酶(PI3K)-蛋白激酶B (PKB或Akt)/哺乳动物雷帕霉素靶蛋白(mTOR)-核糖体蛋白亚基6激酶1(S6K1)/ AMP活化蛋白激酶(AMPK)-过氧化物酶体增殖激活受体共激活剂1α (PGC-1α)通路的改变.

结果:

治疗4周后

与肥胖2型糖尿病大鼠比较

MLZD治疗可明显降低大鼠空腹血糖及胰岛素水平、胰岛素抵抗指数

提高胰岛素敏感指数

并呈现剂量依赖性改变(

0.05). 肥胖2型糖尿病大鼠血清总胆固醇、甘油三酯、低密度脂蛋白胆固醇及游离脂肪酸水平亦明显降低; 脂联素水平升高

瘦素、抵抗素、肿瘤坏死因子-α和白细胞介素-6水平降低(均

0.05或

0.01)

脂肪因子和炎症细胞因子水平得到较大改善. 此外

MLZD可调节PI3K-Akt/mTOR-S6K1/AMPK-PGC-1α通路

保护肝脏和胰腺组织结构.

结论:

MLZD可有效改善糖脂代谢和炎症反应

其作用可能与PI3K-Akt/mTOR-S6K1/AMPK-PGC-1α信号通路有关.

Abstract

Objective:

To investigate the protective effects of modified Linggui Zhugan Decoction (MLZD)

a traditional Chinese medicine formula

on obese type 2 diabetes mellitus (T2DM) rats.

Methods:

Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table

including normal

obese T2DM (ob-T2DM)

MLZD low-dose [MLDZ-L

4.625 g/(kg•d)]

MLZD middle-dose [MLD-M

9.25 g/(kg•d) ] and MLZD high-dose [MLD-H

18.5 g/(kg•d)] groups

10 rats in each group. After 4-week intervention

blood samples and liver

pancreas

muscle tissues were collected to assess the insulin resistance (IR)

blood lipid

adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase (PI3K)- protein kinase B (PKB or Akt)/the mammalian target of rapamycin (mTOR)-ribosome protein subunit 6 kinase 1 (S6K1)/AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) pathways were also studied.

Results:

MLZD dose-dependently reduced fasting blood glucose

fasting insulin

homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2DM rats (

0.05). Similarly

total cholesterol

triglyceride

low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2DM rats after 4-week treatment (

0.05 or

0.01). Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin

resistin

tumor necrosis factor-α and interleukin-6 (

0.05 or

0.01). MLZD regulated the PI3K-Akt/mTOR-S6K1/AMPK-PGC-1α pathways and restored the tissue structure of liver and pancreas (

0.05 or

0.01).

Conclusions:

MLZD ameliorated glycolipid metabolism and inflammation

which may be attributed to the regulation of PI3K-Akt/mTOR-S6K1/AMPK-PGC-1α pathways.

关键词

Keywords

Chinese medicineobesitytype 2 diabetes mellitusglycolipid metabolismadipokinesinflammation

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