Effect of Buyang Huanwu Tang on Myocardial Mitochondrial Energy Metabolism and AMPK/PPARα Signaling Pathway in Rats with Diastolic Heart Failure

Zhen WANG; Jie-bai LI; Xi DONG; Xiao-xu SHEN

doi:10.13422/j.cnki.syfjx.20190902

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Effect of Buyang Huanwu Tang on Myocardial Mitochondrial Energy Metabolism and AMPK/PPARα Signaling Pathway in Rats with Diastolic Heart Failure

Classic Prescriptions | 更新时间：2021-02-09

- Effect of Buyang Huanwu Tang on Myocardial Mitochondrial Energy Metabolism and AMPK/PPARα Signaling Pathway in Rats with Diastolic Heart Failure
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 9, Pages: 12-17(2019)
- 作者机构：
  
  北京中医药大学　东直门医院，北京　 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20190902
  CLC： R2-0; R22; R285.5; R289
- Received：14 September 2018，
  
  Published Online：22 January 2019，
  
  Published：05 May 2019
- 稿件说明：
移动端阅览
Zhen WANG, Jie-bai LI, Xi DONG, et al. Effect of Buyang Huanwu Tang on Myocardial Mitochondrial Energy Metabolism and AMPK/PPARα Signaling Pathway in Rats with Diastolic Heart Failure[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(9): 12-17.
DOI：

Zhen WANG, Jie-bai LI, Xi DONG, et al. Effect of Buyang Huanwu Tang on Myocardial Mitochondrial Energy Metabolism and AMPK/PPARα Signaling Pathway in Rats with Diastolic Heart Failure[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(9): 12-17. DOI： 10.13422/j.cnki.syfjx.20190902.

摘要

目的：

探讨补阳还五汤基于腺苷酸激活蛋白激酶(AMPK)／过氧化物酶体增殖物激活受体

(PPAR

)信号通路对舒张性心衰(DHF)大鼠心肌线粒体能量代谢的影响及其机制研究。

方法：

将48只SD大鼠随机分为假手术组与模型组，模型组大鼠运用腹主动脉缩窄法建立DHF大鼠模型。将造模成功的大鼠随机分为模型组，补阳还五汤组(12.72 g·kg

－1

·d

－1

)，酒石酸美托洛尔组(0.004 5 g·kg

－1

·d

－1

)，灌胃给予相应药物，假手术组、模型组给予等量的去离子水，各组均每日灌胃1次。药物连续干预8周后，采用酶联免疫吸附测定(ELISA)检测大鼠外周血中单磷酸腺苷(AMP)，二磷酸腺苷(ADP)，三磷酸腺苷(ATP)的含量；采用投射电镜检测心肌线粒体超微结构的变化；采用蛋白免疫印迹法(Western blot)检测大鼠心肌组织中AMPK

PPAR

，PPAR

辅助激活因子1

(PGC-1

)的蛋白表达量。

结果：

与假手术组比较，模型组大鼠AMP

ADP含量显著升高，ATP含量显著下降(

0.05，

0.01)；与模型组比较，补阳还五汤组、酒石酸美托洛尔组大鼠AMP含量明显降低(

0.01)，ADP含量下降(

0.05)，ATP含量升高。与假手术组比较，模型组大鼠线粒体数量减少，形态异常；与模型组比较，补阳还五汤组、酒石酸美托洛尔组大鼠线粒体数量明显增加，形态明显改善。与假手术组比较，各组大鼠AMPK蛋白表达量无统计学差异；与假手术组比较，模型组PPAR

，PGC-1

蛋白表达水平明显降低(

0.05)。与模型组比较，补阳还五汤组、酒石酸美托洛尔组PPAR

，PGC-1

蛋白表达水平明显升高(

0.05)。

结论：

补阳还五汤可能是通过改善线粒体结构和功能，激活AMPK并上调AMPK/PPAR

信号通路的表达，从而改善衰竭心脏的能量代谢，延缓心衰进展。

Abstract

Objective:

To study the effect of Buyang Huanwu Tang on myocardial energy metabolism in rats with diastolic heart failure (DHF) based on adenosine monophosphate (AMP)-activated protein kinase(AMPK)/peroxisome proliferators-activated receptors

(PPAR

) signaling pathway

and investigate its mechanism of action.

Method:

The 48 SD rats were randomly divided into sham operation group and model group. DHF rat model was established by abdominal aorta constriction method. The successfully modeled rats were randomly divided into model group

Buyang Huanwu Tang group (12.72 g·kg

-1

·d

-1

)

metoprolol tartrate group (0.004 5 g·kg

-1

·d

-1

)

with corresponding drugs in each group by intragastric administration. The sham operation group and model group were given with equal amount of deionized water

once a day. After 8 weeks of continuous drug intervention

the contents of adenosine monophosphate (AMP)

adenosine diphosphate (ADP) and adenosine triphophate (ATP) in peripheral blood of rats were determined by enzyme linked immunosorbent assay (ELISA). The changes of myocardial mitochondrial ultrastructure were detected by electron microscope. The protein expression levels of AMPK

PPAR

and peroxisome proliferator-activated receptor-

coactivator-1

(PGC-1

) in rat myocardium were detected by Western blot.

Result:

As compared with sham operation group

the contents of AMP and ADP in model group were increased significantly

and ATP content was decreased significantly (

0.05

0.01). As compared with the model group

the AMP content was decreased significantly in Buyang Huanwu Tang group and metoprolol tartrate group (

0.01)

and the content of ADP was decreased while ATP content was increased(

0.05). As compared with the sham operation group

the number of mitochondria in the model group was decreased

the morphology was abnormal; as compared with the model group

the number of mitochondria in Buyang Huanwu Tang group and metoprolol tartrate group was increased obviously

and the morphology was obviously improved. As compared with the sham operation group

there was no statistically significant difference in the expression of AMPK protein between various groups

but the expression levels of PPAR

and PGC-1

protein in the model group were decreased significantly(

0.05). As compared with the model group

the expression levels of PPAR

and PGC-1

protein in Buyang Huanwu Tang group and metoprolol tartrate group were increased significantly (

0.05).

Conclusion:

Buyang Huanwu Tang may improve the energy metabolism of the failed heart and delay the progression of heart failure by improving the structure and function of mitochondria

activating AMPK and up-regulating the expression of AMPK/PPAR

signaling pathway.

关键词

Keywords

references

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