Muscone improves coronary microvascular disease by promoting VEGF-mediated microvascular angiogenesis

WANG Ziyang; TIAN Dingyuan; ZHENG Pan; CHEN Ming; ZHENG Zimeng; DENG Fang; ZHANG Zhihui

doi:10.16016/j.2097-0927.202508058

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Muscone improves coronary microvascular disease by promoting VEGF-mediated microvascular angiogenesis

Basic Medicine | 更新时间：2025-10-13

- Muscone improves coronary microvascular disease by promoting VEGF-mediated microvascular angiogenesis
- Journal of Army Medical University Vol. 47, Issue 19, Pages: 2374-2384(2025)
- 作者机构：
  
  1.陆军军医大学（第三军医大学）：第一附属医院心血管内科
  2.陆军军医大学（第三军医大学）：高原军事医学系病理生理学教研室
- 作者简介：
- 基金信息：
  
  the Special Project of Technological Innovation and Application Development of Chongqing(CSTB2023TIAD-KPX0061-2)
- DOI：10.16016/j.2097-0927.202508058
  CLC： R285.5;R289.5;R543.3
- Received：19 August 2025，
  
  Revised：2025-09-15，
  
  Accepted：15 September 2025，
  
  Published：15 October 2025
- 稿件说明：
移动端阅览
汪紫阳，田丁元，郑攀，等.麝香酮通过促进VEGF表达介导的微血管生成改善冠状动脉微血管疾病［J］.陆军军医大学学报，2025，47（19）：2374-2384.DOI：10.16016/j.2097-0927.202508058.

WANG Z Y，TIAN D Y，ZHENG P，et al.Muscone improves coronary microvascular disease by promoting VEGF-mediated microvascular angiogenesis［J］.J Army Med Univ，2025，47（19）：2374-2384.DOI：10.16016/j.2097-0927.202508058.
汪紫阳，田丁元，郑攀，等.麝香酮通过促进VEGF表达介导的微血管生成改善冠状动脉微血管疾病［J］.陆军军医大学学报，2025，47（19）：2374-2384.DOI：10.16016/j.2097-0927.202508058. DOI：

WANG Z Y，TIAN D Y，ZHENG P，et al.Muscone improves coronary microvascular disease by promoting VEGF-mediated microvascular angiogenesis［J］.J Army Med Univ，2025，47（19）：2374-2384.DOI：10.16016/j.2097-0927.202508058. DOI：

摘要

目的

探讨麝香保心丸（shexiang baoxin pill， SXBXP）对冠状动脉微血管疾病（coronary microvascular disease，CMD）的影响以及麝香酮（Muscone）作为SXBXP中的有效成分对CMD的作用及机制。

方法

8周龄的ob/ob小鼠按照每天10 mg/kg SXBXP（SXBXP组）或无菌PBS（Ctl组）进行灌胃，同背景野生型小鼠（WT组）作为阴性对照；以缺血缺氧干预小鼠冠脉微血管内皮细胞（mouse coronary microvascular endothelial cell，MCMEC）构建CMD细胞模型（HI组），并以20 μg/mL浓度的SXBXP（HI+SX）和30 μmol/L浓度的Muscone（HI+Muscone）分别进行药物干预。通过心脏超声动态评估冠状动脉血流储备（coronary flow reserve，CFR）水平和左心室功能，激光散斑成像评估心肌血流量（myocardial blood flow，MBF）水平。通过CD31免疫荧光染色评估小鼠心脏微血管密度。通过免疫荧光染色和Western blot检测心脏微血管内皮细胞的血管内皮生长因子（Vascular endothelial growth factor，VEGF）表达。5-乙炔基-2-脱氧嘧啶核苷染色、血管生成实验检测MCMEC的增殖能力和成管能力。

结果

ob/ob-Control组小鼠CFR、MBF水平和心脏微血管密度均比WT组小鼠显著降低（

0.01），ob/ob-SXBXP 组小鼠的上述指标均显著高于ob/ob对照组（

0.05），表明SXBXP对CMD表型具有改善作用。ob/ob-Control组小鼠心脏微血管内皮细胞VEGF表达水平比WT组小鼠显著降低（

0.05），而ob/ob-SXBXP组小鼠心脏微血管内皮细胞VEGF表达水平显著高于ob/ob-Control组（

0.05），SXBXP可能通过VEGF介导的微血管生成改善CMD。体外实验进一步显示，缺血缺氧组（HI）组的VEGF表达水平及MCMEC的增殖和成管能力均显著低于常氧培养（Ctl组）（

0.05），缺血缺氧SXBXP干预组（HI+SX）和缺血缺氧Muscone干预组（HI+Muscone）上述指标均显著高于HI组（

0.05），Muscone作为SXBXP的活性物质通过VEGF介导的微血管生成改善CMD。

结论

SXBXP对CMD具有改善作用；Muscone 作为SXBXP中的主要成分通过诱导VEGF的表达促进冠状动脉微血管生成，增加心肌灌注水平从而改善CMD。

Abstract

Objective

To explore the impact of Shexiang Baoxin Pill (SXBXP

a traditional Chinese patent medicine

broadly applied for the treatment of cardiovascular diseases) on coronary microvascular disease (CMD) and investigate the role and underlying mechanisms of muscone

a key bioactive component of the pills

in the treatment.

Methods

A total of 16 ob/ob mice (8 weeks old) were randomly and equally divided into an ob/ob-SXBXP group and a ob/ob-Control group

receiving 10 mg/kg·d SXBXP or PBS

via

oral gavage

and another 8 wild-type mice with the same genetic background (WT group) were subjected as a negative control group. Cell model of CMD was established based on mouse coronary microvascular endothelial cells (MCMEC) under ischemia and hypoxic (HI) condition

and the cells were further treated with 20 μg/mL SXBXP (HI+SX) and 30 μmol/L muscone (HI+Muscone)

respectively. Echocardiography was carried out for coronary flow reserve (CFR) and left ventricular function

and laser speckle

imaging was applied to evaluate myocardial blood flow (MBF). Microvascular density in the heart was evaluated with CD31 immunofluorescence staining. The expression levels of vascular endothelial growth factor (VEGF) in cardiac microvascular endothelial cells of both mouse and cell models were detected by immunofluorescence staining and Western blot analysis. The proliferation and angiogenesis of MCMEC were observed by 5-ethynyl-2'-deoxyuridine staining and angiogenesis experiments.

Results

In the ob/ob-Control group of mice

the levels of CFR

MBF

and cardiac microvascular density were significantly lower than those in the WT group (

0.05)

and these indicators were significantly improved in the ob/ob-SXBXP group when compared with the ob/ob-Control group (

0.05)

which indicates that SXBXP improves the CMD phenotype. The expression level of VEGF in cardiac microvascular endothelial cells was significantly lower in the ob/ob-Control mice than the WT mice (

0.05)

while the level in the ob/ob-SXBXP group was significantly higher than that in the ob/ob-Control group (

0.05)

illustrating that SXBXP may ameliorate CMD through VEGF-mediated microvascular angiogenesis.

In vitro

experiments further revealed that the VEGF expression level and the proliferation and angiogenesis abilities in MCMEC were significantly lower in the HI group than the cells under the normoxia control condition (

0.05). Both SXBXP and muscone treatment resulted in enhanced expression of VEGF and improved proliferative and angiogenesis abilities of MCMEC (

0.05). These results suggest that muscone could improve CMD by VEGF-mediated microvascular angiogenesis.

Conclusion

SXBXP can improve CMD. Muscone

as a key component of SXBXP

promotes microvascular angiogenesis by inducing the expression of VEGF

then enhances myocardial perfusion

and consequently alleviates CMD.

关键词

Keywords

references

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