基于AMPK/ACC信号通路探讨夏枯草提取物调节ZDF大鼠脂代谢的机制

田硕; 吴丽丽; 张卫华; 董笑克; 韩艺凡; 洪明昭

doi:10.13422/j.cnki.syfjx.20190806

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基于AMPK/ACC信号通路探讨夏枯草提取物调节ZDF大鼠脂代谢的机制

药理 | 更新时间：2021-02-09

- 基于AMPK/ACC信号通路探讨夏枯草提取物调节ZDF大鼠脂代谢的机制
- Mechanism of Prunellae Spica Extracts on Lipid Metabolism in ZDF Rats Based on AMPK/ACC Signalling Pathway
- 中国实验方剂学杂志 2019年25卷第9期页码：82-88
- 作者机构：
  
  1.北京中医药大学　教育部中医养生学重点实验室，北京　 100029
  2.北京宝德润生医药科技发展有限公司，北京　 100088
  3.北京中医药大学　东方医院，北京　 100078
  4.深圳市光明新区人民医院，广东　深圳　 518106
- 作者简介：
  
  田硕，硕士，从事中医药防治糖尿病及其并发症的临床和基础研究，E-mail：583049134@qq.com
  吴丽丽，博士，助理研究员，从事中医药防治糖尿病及其并发症的临床和基础研究，Tel：010-64286950，E-mail：qingniao_566@163.com；
  张卫华，硕士，高级工程师，从事中药新剂型、中药新药、中药保健食品研究开发，E-mail：strong_ng_zzz@163.com
- 基金信息：
  
  北京中医药大学2018年度基本科研业务费重点实验室项目(2018-JYB-JS)
- DOI：10.13422/j.cnki.syfjx.20190806
  中图分类号： R2-0; R22; R285.5
- 收稿日期：2018-08-12，
  
  网络出版日期：2019-01-03，
  
  纸质出版日期：2019-05-05
- 稿件说明：
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田硕, 吴丽丽, 张卫华, 等. 基于AMPK/ACC信号通路探讨夏枯草提取物调节ZDF大鼠脂代谢的机制[J]. 中国实验方剂学杂志, 2019,25(9):82-88.

Shuo TIAN, Li-li WU, Wei-hua ZHANG, et al. Mechanism of Prunellae Spica Extracts on Lipid Metabolism in ZDF Rats Based on AMPK/ACC Signalling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(9): 82-88.
田硕, 吴丽丽, 张卫华, 等. 基于AMPK/ACC信号通路探讨夏枯草提取物调节ZDF大鼠脂代谢的机制[J]. 中国实验方剂学杂志, 2019,25(9):82-88. DOI： 10.13422/j.cnki.syfjx.20190806.

Shuo TIAN, Li-li WU, Wei-hua ZHANG, et al. Mechanism of Prunellae Spica Extracts on Lipid Metabolism in ZDF Rats Based on AMPK/ACC Signalling Pathway[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(9): 82-88. DOI： 10.13422/j.cnki.syfjx.20190806.

摘要

目的：

观察夏枯草提取物(Prunellae Spica extracts

PS)对Zucker糖尿病肥胖(ZDF)模型大鼠肝腺苷酸活化蛋白激酶(AMPK)／乙酰辅酶A羧化酶(ACC)信号通路的影响以探讨其改善大鼠脂代谢的机制。

方法：

32只雄性ZDF(fa/fa)2型糖尿病模型大鼠随机分为模型组、二甲双胍组(180 mg·kg

－1

·d

－1

)和PS低、高剂量组(12.25，24.5 mg·kg

－1

·d

－1

)，每组8只。8只Zuker Lean(ZL)大鼠设为正常组。于给药0，4，8周测体质量及空腹血糖。给药8周后，腹主动脉取血，离心抽取血清－20 ℃冻存，取肝组织－80 ℃冻存，及4%多聚甲醛固定，石蜡包埋。放射免疫法测血清甘油三酯(TG)，胆固醇(CHO)，低密度脂蛋白胆固醇(LDL-C)及游离脂肪酸(FFA)。油红O染色观察肝细胞脂滴含量。实时荧光定量聚合酶链式反应(Real-time PCR)检测肝脏AMPK

及ACC mRNA表达。免疫组化法测肝细胞磷酸化(p)-AMPK

蛋白表达。

结果：

与正常组比较，模型组大鼠血清TG

CHO

LDL-C及FFA升高，肝细胞脂滴增加，肝AMPK

mRNA表达减少而ACC1和ACC2 mRNA表达增加，p-AMPK

蛋白表达减少(

0.05，

0.01)。与模型组比较，PS低、高剂量组可明显降低ZDF大鼠血清TG

CHO

LDL-C及FFA，减少肝细胞脂滴，上调肝AMPK

mRNA且下调ACC1和ACC2 mRNA表达，上调p-AMPK

蛋白表达(

0.05，

0.01)。

结论：

PS能有效改善2型糖尿病ZDF大鼠肝脏脂代谢紊乱，其机制可能与调节肝AMPK/ACC信号通路有关。

Abstract

Objective:

To observe the effect of Prunellae Spica extracts (PS) on the lipid metabolism in Zuker Diabetes Fatty (ZDF) rats based on AMP-activated protein kinase/acetyl CoA carboxylase(AMPK/ACC) signaling pathway.

Method:

The 32 male ZDF (fa/fa) type 2 diabetic rats were randomly divided into model group

metformin group (180 mg·kg

-1

·d

-1

)

and low and high-dose PS groups (12.25

24.5 mg·kg

-1

·d

-1

)

with 8 in each group. 8 male Zuker Lean (ZL) rats were selected as normal group. Body weight and fasting blood glucose were monitored at the 0

and 8

weeks after administration. After 8 weeks

abdominal aorta blood was collected

serum was frozen at -20 ℃ by centrifugation

liver tissue was frozen at -80 ℃

fixed with 4%paraformaldehyde and embedded in paraffin. Serum triglyceride (TG)

cholesterol (CHO)

low density lipoprotein cholesterol (LDL-C) and free fatty acid (FFA) levels were measured by radioimmunoassay. Fat droplets in hepatocytes were measured by oil red O staining. Gene expressions of AMP-activated protein kinase-alpha 2 (AMPK

)

Acetyl CoA carboxylase (ACC) in liver were detected by real-time polymerase chain reaction (Real-time PCR). Protein expressions of p-AMPK

were observed by immuno-histochemical (IHC) method.

Result:

Compared with the normal group

the T2DM model group showed significant increases in serum levels of TG

CHO

LDL-C

FFA and lipid droplets in hepatocytes. AMPK

mRNA expression was decreased

while ACC1 and ACC2 mRNA expressions were increased significantly. p-AMPK

protein expression in liver was decreased significantly (

0.05

0.01). Compared with the model group

low and high-dose Ps groups showed significant decreases in serum levels of TG

CHO

LDL-C

FFA and lipid droplets in hepatocytes in ZDF rats

up-regulation in mRNA expression of AMPK

down-regulation in mRNA expressions of ACC1 and ACC2

and up-regulation in protein expression of p-AMPK

(

0.05

0.01).

Conclusion:

PS can effectively improve liver lipid metabolism in ZDF rats. Its mechanism may be related to the regulation of AMPK/ACC signaling pathway in liver.

关键词

Keywords

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