Effect of <italic style="font-style: italic">Jianxin Granules </italic>（健心颗粒） on Myocardial Energy Metabolism and PPARα/PGC-1α Pathway in Model Rats of Chronic Heart Failure with <italic style="font-style: italic">Qi</italic> Deficiency and Blood Stasis Syndrome

CHEN Juan; HUANG Feixiang; WANG Yong; ZHOU Yiwei; CHEN Meihua; YE Ying

doi:10.13288/j.11-2166/r.2023.04.014

您当前的位置：

首页 >

文章列表页 >

Effect of Jianxin Granules （健心颗粒） on Myocardial Energy Metabolism and PPARα/PGC-1α Pathway in Model Rats of Chronic Heart Failure with Qi Deficiency and Blood Stasis Syndrome

更新时间：2023-02-14

- Effect of Jianxin Granules （健心颗粒） on Myocardial Energy Metabolism and PPARα/PGC-1α Pathway in Model Rats of Chronic Heart Failure with Qi Deficiency and Blood Stasis Syndrome
- Journal of Traditional Chinese Medicine Vol. 64, Issue 4, Pages: 393-400(2023)
- 作者机构：
  
  福建中医药大学附属第二人民医院，福建省福州市五四路282号，350000
- 作者简介：
- 基金信息：
- DOI：10.13288/j.11-2166/r.2023.04.014
  CLC：
- Received：18 April 2022，
  
  Revised：2022-11-10，
  
  Published：17 February 2023
- 稿件说明：
移动端阅览
陈隽,黄飞翔,王永等.健心颗粒对慢性心力衰竭气虚血瘀证模型大鼠心肌能量代谢及PPARα/PGC-1α通路的影响[J].中医杂志,2023,64(04):393-400.

CHEN Juan,HUANG Feixiang,WANG Yong,et al.Effect of Jianxin Granules （健心颗粒） on Myocardial Energy Metabolism and PPARα/PGC-1α Pathway in Model Rats of Chronic Heart Failure with Qi Deficiency and Blood Stasis Syndrome[J].Journal of Traditional Chinese Medicine,2023,64(04):393-400.
陈隽,黄飞翔,王永等.健心颗粒对慢性心力衰竭气虚血瘀证模型大鼠心肌能量代谢及PPARα/PGC-1α通路的影响[J].中医杂志,2023,64(04):393-400. DOI： 10.13288/j.11-2166/r.2023.04.014.

CHEN Juan,HUANG Feixiang,WANG Yong,et al.Effect of Jianxin Granules （健心颗粒） on Myocardial Energy Metabolism and PPARα/PGC-1α Pathway in Model Rats of Chronic Heart Failure with Qi Deficiency and Blood Stasis Syndrome[J].Journal of Traditional Chinese Medicine,2023,64(04):393-400. DOI： 10.13288/j.11-2166/r.2023.04.014.

摘要

目的

从心肌能量代谢角度探讨健心颗粒治疗慢性心力衰竭气虚血瘀证的可能作用机制。

方法

60只SD大鼠随机分为造模组50只和空白组10只。造模组大鼠采用冠脉结扎配合力竭式游泳、饥饿法建立慢性心力衰竭气虚血瘀证模型。造模成功46只大鼠随机分为模型组10只，缬沙坦组及健心颗粒低、中、高剂量组各9只。缬沙坦组给予7.2 mg/（kg·d）缬沙坦灌胃，健心颗粒低、中、高剂量组分别给予1.6、3.2、6.4 g/（kg·d）剂量的健心颗粒灌胃，模型组和空白组每天仅给予1 ml/100 g无菌生理盐水灌胃。各组均每天灌胃2次，共4周。HE和Masson染色观察大鼠心肌组织病理改变。检测大鼠心肌组织能量代谢指标［包括糖原质量分数、脂肪酸（FA）及乳酸浓度、三磷酸腺苷（ATP）浓度］、左室射血分数（EF）、心肌组织过氧化物酶体增殖物激活受体α（PPARα）、过氧化物酶体增殖物激活受体γ辅助活化因子-1α（PGC-1α）、300 KDA腺病毒E1A结合蛋白（P300）、中链酰基辅酶A脱氢酶（MCAD）、腺苷酸转运体（ANT）蛋白及mRNA表达。

结果

HE和Masson染色结果显示，模型组大鼠心肌细胞重度肥大、排列松散，心肌纤维断裂，成纤维细胞严重增生并伴有炎细胞浸润，心肌纤维化严重，胶原组织增生明显，缬沙坦组和健心颗粒各剂量组心肌组织损伤和胶原组织增生均有不同程度改善。与空白组比较，其余各组大鼠心肌组织FA和乳酸浓度升高，EF、糖原质量分数、ATP浓度和PPARα、PGC-1α、P300、MCAD、ANT mRNA及蛋白表达降低（

＜0.05）；与模型组比较，缬沙坦组和健心颗粒各剂量组心肌组织FA和乳酸浓度降低，EF、糖原质量分数、ATP浓度和PPARα、PGC-1α、P300、MCAD、ANT mRNA及蛋白表达升高（

＜0.05）；且健心颗粒高剂量组各指标改善优于缬沙坦组和健心颗粒低、中剂量组（

＜0.05），健心颗粒中剂量组各指标改善与缬沙坦组比较差异无统计学意义（

＞0.05）。

结论

健心颗粒可显著改善慢性心力衰竭气虚血瘀证大鼠心肌能量代谢，且以高剂量最佳，推测其可能是通过调控PPARα/PGC-1α通路而实现。

Abstract

Objective

To investigate the potential mechanism of

Jianxin Granules

（健心颗粒） in the treatment of chronic heart failure （CHF） with

deficiency and blood stasis syndrome from the perspective of myocardial energy metabolism.

Methods

Sixty SD rats were randomly divided into modeling group （n=50） and blank group （n=10）. The former established the rat model of CHF with

deficiency and blood stasis syndrome by coronary artery ligation combined with exhaustive swimming and starvation. Forty-six rats were successfully modeled and were divided into model group （n=10）， valsartan group （n=9） and

Jianxin Granules

low-， medium- and high-dose groups （n=9 each） according to the random number table. Valsartan group was given 7.2 mg /（kg·d） of valsartan by gavage， while the low-， medium- and high-dose groups of

Jianxin Granules

were given 1.6， 3.2 and 6.4g/（kg·d） of

Jianxin Granules

by gavage， respectively. The model group and the blank group were given 1 ml/100 g of sterile normal saline by gavage. The above interventions were administered twice a day for 4 weeks. Hematoxylin eosin （HE） and Masson staining were used to observe the pathological changes of rat myocardial tissue. The indexes of energy metabolism in rat myocardial tissues including glycogen mass fraction， concentration of fatty acid （FA） and lactic acid， and adenosine triphosphate （ATP） concentration were measured. Left ventricular ejection fraction （EF）， peroxisome proliferator activated receptor α （PPARα）， peroxisome proliferator activated receptor γ coactivator-1α （PGC-1α）， 300kda adenovirus E1A binding protein （P300）， medium chain acyl CoA dehydrogenase （MCAD） and adenylate transporter （ANT） proteins and mRNA expressions were detected.

Results

HE and Masson staining showed that in the model group， cardiomyocytes were severely hypertrophic and loosely arranged， with broken myocardial fibers， seriously proliferated fibroblasts accompanied by inflammatory cell infiltration， as well as serious myocardial fibrosis and obvious collagen tissue hyperplasia. The myocardial tissues injury and collagen tissue hyperplasia in valsartan group and all three

Jianxin Granules

groups were improved in varying degrees. Compared to those in the blank group， the concentration of FA and lactic acid in myocardial tissues increased， and EF， glycogen mass fraction， ATP concentration， and the mRNA and protein expressions of PPARα， PGC-1α， P300， MCAD and ANT decreased in the model group， valsartan group and three

Jianxin Granules

groups （

＜0.05）. Compared to those in the model group， the concentration of FA and lactic acid in myocardial tissues decreased， and EF， mass fraction of glycogen， ATP concentration and the mRNA and protein expressions of PPARα， PGC-1α， P300， MCAD and ANT in the valsartan group and

Jianxin Granules

groups increased （

＜0.05）. More changes were found in the high-dose

Jianxin Granules

group than the low- and medium-dose groups （

＜0.05）. The differences were not statistically significant in the mentioned indexes between the medium-dose

Jianxin Granules

group and the valsartan group （

＞0.05）.

Conclusion

Jianxin Granules

can improve myocardial energy metabolism in CHF rats with

deficiency and blood stasis syndrome， presumably by regulating PPARα/PGC-1α pathway. And the high-dose

Jianxin Granules

shows best effect.

关键词

Keywords

references

MCDONAGH TA ， METRA M ， ADAMO M ， et al . 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure ［J］. Eur Heart J ， 2021 ， 42 （ 36 ）： 3599 - 3726 .

徐佳慧，胡世莲 . 慢性心力衰竭的流行病学与预防措施［J］. 中国临床保健杂志， 2021 ， 24 （ 6 ）： 721 - 725 .

KIMBALL TH ， VONDRISKA TM . Metabolism， epigenetics， and causal inference in heart failure ［J］. Trends Endocrinol Metab ， 2020 ， 31 （ 3 ）： 181 - 191 .

王理亚，单艳华，刘永萍，等 . PPAR-α的激活对心力衰竭早期心肌功能的机制研究［J］. 安徽医药， 2022 ， 26 （ 4 ）： 754 - 759， 850 .

TIAN L ， CAO W ， YUE R ， et al . Pretreatment with Tilianin improves mitochondrial energy metabolism and oxidative stress in rats with myocardial ischemia/reperfusion injury via AMPK/SIRT1/PGC-1 alpha signaling pathway ［J］. J Pharmacol Sci ， 2019 ， 139 （ 4 ）： 352 - 360 .

王巍，罗玉寅，廖骏 . 活血通脉方对慢性心力衰竭大鼠心肌纤维化和心肌细胞能量代谢的影响研究［J］. 新中医， 2020 ， 52 （ 22 ）： 1 - 5 .

ANCION A ， NGUYEN TRUNG ML ， TRIDETTI J ， et al . Therapeutic revolution in heart failure ［J］. Rev Med Liege ， 2020 ， 75 （ 5/6 ）： 304 - 309 .

黄飞翔，许杨，叶盈，等 . 健心颗粒干预左室射血分数正常的心衰临床研究［J］. 中西医结合心脑血管病杂志， 2012 ， 10 （ 10 ）： 1155 - 1157 .

柏义泊，陈成，张旺生，等 . 健心颗粒治疗老年气虚血瘀型慢性心力衰竭临床观察［J］. 山西中医， 2021 ， 37 （ 10 ）： 14 - 16 .

林清，郭佳和，徐航晨，等 . 健心颗粒对慢性心力衰竭病人血浆可溶性ST2水平的影响［J］. 中西医结合心脑血管病杂志， 2019 ， 17 （ 12 ）： 1835 - 1837 .

张艳，方素清，姜凯，等 . 慢性心衰气虚血瘀证大鼠模型的研究初探［J］. 中国中医药信息杂志， 2006 ， 13 （ 8 ）： 14 - 15 .

温剑艺，谭宁，杨大浩 . 大鼠心肌缺血-再灌注模型的心电图变化［J］. 岭南心血管病杂志， 2011 ， 17 （ 6 ）： 503 - 506 .

XU P ， WANG Y ， SUN W ， et al . Salidroside protects the cardiac function of exhausted rats by inducing Nrf2 expression ［J］. Cardiovasc J Afr ， 2020 ， 31 （ 1 ）： 25 - 32 .

赵倩倩 . 改良冠脉结扎术制备大鼠慢性心衰模型［J］. 生物化工， 2019 ， 5 （ 4 ）： 51 - 53 .

徐叔云．药理实验方法学［M］．北京：人民卫生出版社， 2002 ： 911 ．

来晓磊，尚菊菊，刘红旭，等 . 泻肺利水合剂联合西医常规方法治疗慢性缺血性心力衰竭气虚血瘀证疗效的真实世界、多中心、队列研究［J］. 中医杂志， 2022 ， 63 （ 6 ）： 544 - 550 .

苏天生，肖章武，卢静，等 . 健心颗粒对心力衰竭大鼠模型心肌代谢重构的作用［J］. 中国医药科学， 2022 ， 12 （ 13 ）： 36 - 39， 81 .

LOPASCHUK GD ， KARWI QG ， TIAN R ， et al . Cardiac energy metabolism in heart failure ［J］. Circ Res ， 2021 ， 128 （ 10 ）： 1487 - 1513 .

BADOLIA R ， RAMADURAI DKA ， ABEL ED ， et al . The role of nonglycolytic glucose metabolism in myocardial recovery upon mechanical unloading and circulatory support in chronic heart failure ［J］. Circulation ， 2020 ， 142 （ 3 ）： 259 - 274 .

GENTILE F ， SCIARRONE P ， ZAMORA E ， et al . Body mass index and outcomes in ischaemic versus non-ischaemic heart failure across the spectrum of ejection fraction ［J］. Eur J Prev Cardiol ， 2021 ， 28 （ 9 ）： 948 - 955 .

JAO TM ， NANGAKU M ， WU CH ， et al . ATF6α downregulation of PPARα promotes lipotoxicity-induced tubulointerstitial fibrosis ［J］. Kidney Int ， 2019 ， 95 （ 3 ）： 577 - 589 .

PUCA F ， YU F ， BARTOLACCI C ， et al . Medium-chain acyl-CoA dehydrogenase protects mitochondria from lipid peroxidation in glioblastoma ［J］. cancer discov ， 2021 ， 11 （ 11 ）： 2904 - 2923 .

BHAT S ， CHIN A ， SHIRAKABE A ， et al . Recruitment of RNA polymerase ii to metabolic gene promoters is inhibited in the failing heart possibly through pgc-1α （peroxisome proliferator-activated receptor-γ coactivator-1α） dysregulation ［J］. Circ Heart Fail ， 2019 ， 12 （ 3 ）： e005529 .

KREITER J ， RUPPRECHT A ， ŠKULJ S ， et al . ANT1 activation and inhibition patterns support the fatty acid cycling mechanism for proton transport ［J］. Int J Mol Sci ， 2021 ， 22 （ 5 ）： 2490 .

YANG Y ， ZHANG H ， LI X ， et al . Effects of PPARα/PGC-1α on the myocardial energy metabolism during heart failure in the doxorubicin induced dilated cardiomyopathy in mice ［J］. Int J Clin Exp Med ， 2014 ， 7 （ 9 ）： 2435 - 2442 .

查看原文

Views

下载量

CSCD

Alert me when the article has been cited

提交

Tools

Publicity Resources

Overview of Study on Syndromic Characteristics and Microscopic Indicators of Qi Deficiency and Blood Stasis Syndrome in Chronic Heart Failure

Effect of Shengjie Tongyu Decoction （升解通瘀汤） on Urine Metabolomics in Patients with Ischemic Cardiomyopathy-induced Chronic Heart Failure and Qi Deficiency and Blood Stasis Syndrome

Effect of Xingeng No.Ⅱ Granules （心梗2号颗粒剂） on Left Ventricular Remodeling in Patients of ST-Segment Elevation Myocardial Infarction with Qi Deficiency and Blood Stasis Syndrome after PCI：An Open-Labbled Randomized-Controlled Trial

Effect of Shenqi Jianxin Formula（参芪健心方）on Mitochondrial Autophagy and the PINK1/Parkin Signaling Pathway in Cardiac Tissues in Chronic Heart Failure

Effect of Optimized New Shengmai Powder （优化新生脉散方） on Exercise Tolerance in Patients with Chronic Heart Failure of Qi Deficiency，Blood Stasis and Fluid Retention Syndrome：A Randomized，Double-Blind，Placebo-Controlled Trial

Related Author

MENG Lichong

TAN Duoting

WANG Ziyi

LI Lin

HU Zhixi

SUN Ziyi

YAO Kuiwu

WANG Zihan

Related Institution

Hunan University of Chinese Medicine

Hunan Academy of Chinese Medicine

Guang'anmen Hospital，China Academy of Chinese Medical Sciences

Beijing University of Chinese Medicine

Eye Hospital, China Academy of Chinese Medical Sciences

Address：No.16, Nanxiao street, Dongzhimen, Dongcheng District, Beijing Postal code：100700
Tel：010-64035632 Email：jtcmcn@188.com
Technical support is provided by Beijing Founder electronics co., LTD 京ICP备09064830号-19 京公网安备11010102007558号
It is recommended to read the content of this site in Chrome&IE9+. Please switch to extreme mode in browser 360.
Cookies We use cookies to help provide and enhance our service and tailor content. By continuing, you agree to the use of cookies.

⁰

Effect of Jianxin Granules （健心颗粒） on Myocardial Energy Metabolism and PPARα/PGC-1α Pathway in Model Rats of Chronic Heart Failure with Qi Deficiency and Blood Stasis Syndrome

DOI：10.13288/j.11-2166/r.2023.04.014

摘要

Abstract

关键词

Keywords

references