参麦注射液通过miR-30a/Bcl-2减轻阿霉素诱导的心肌细胞凋亡

ZHANG Xiao-nan; LI Yan-yang; LYU Shi-chao; JIA Qiu-jin; ZHANG Jun-ping; LIU Long-tao

doi:10.1007/s11655-025-4005-8

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参麦注射液通过miR-30a/Bcl-2减轻阿霉素诱导的心肌细胞凋亡

Original Article | Updated：2025-02-24

- 参麦注射液通过miR-30a/Bcl-2减轻阿霉素诱导的心肌细胞凋亡
- Shenmai Injection Reduces Cardiomyocyte Apoptosis Induced by Doxorubicin through miR-30a/Bcl-2
- 中国结合医学杂志（英文版） 2025年31卷第3期页码：240-250
- Affiliations：
  
  1.Department of Cardiovascular Medicine, National Clinical Research Center for Chinese Medicine Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing (100091), China
  2.Department of Integrated Traditional Chinese and Western Medicine, Tianjin Medical University Cancer Institute and Hospital, Tianjin (300060), China
  3.Department of Cardiovascular Medicine, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin (300193), China
  4.Department of Cardiovascular Medicine, Tianjin Key Laboratory of Traditional Research of Traditional Chinese Medicine Prescription and Syndrome, Tianjin (300193), China
- Author bio：
  
  Prof. LIU Long-tao, E-mail: liulongtao1976@126.com
- Funds：
  
  the National Natural Science Foundation of China(81904118);Hospital Capability Enhancement Project of Xiyuan Hospital, China Academy of Chinese Medical Sciences(XYZX0201-09);the Special Programme for the Cultivation of Outstanding Young Scientific and Technological Talents of the China Academy of Chinese Medical Sciences(ZZ17-YQ-005)
- DOI：10.1007/s11655-025-4005-8
  中图分类号：
- 录用日期：2024-11-11，
  
  网络出版日期：2025-01-15，
  
  纸质出版日期：2025-03
- Accepted：
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参麦注射液通过miR-30a/Bcl-2减轻阿霉素诱导的心肌细胞凋亡[J]. 中国结合医学杂志（英文版）, 2025,31(3):240-250.

ZHANG Xiao-nan, LI Yan-yang, LYU Shi-chao, et al. Shenmai Injection Reduces Cardiomyocyte Apoptosis Induced by Doxorubicin through miR-30a/Bcl-2[J]. Chinese journal of integrative medicine, 2025, 31(3): 240-250.
参麦注射液通过miR-30a/Bcl-2减轻阿霉素诱导的心肌细胞凋亡[J]. 中国结合医学杂志（英文版）, 2025,31(3):240-250. DOI： 10.1007/s11655-025-4005-8.

ZHANG Xiao-nan, LI Yan-yang, LYU Shi-chao, et al. Shenmai Injection Reduces Cardiomyocyte Apoptosis Induced by Doxorubicin through miR-30a/Bcl-2[J]. Chinese journal of integrative medicine, 2025, 31(3): 240-250. DOI： 10.1007/s11655-025-4005-8.

摘要

目的:

探讨参麦注射液 (SMI) 对阿霉素 (DOX) 诱导的心肌细胞凋亡的分子机制.

方法:

选取40只SPF级雄性Sprague Dawley (SD) 大鼠

根据随机数字表法分为5组

分别为对照组、模型组、miR-30a激动剂组、参麦注射液低剂量 (SMI-L) 组和参麦注射液高剂量 (SMI-H) 组

每组8只. 除对照组外

余各组大鼠每周经尾静脉注射DOX (2mg/kg)

连续4周诱导心肌损伤

并给予不同方案连续干预2周. 通过超声心动图检测心功能

采用Van Gieson (VG) 染色观察心肌病理变化; 通过酶联免疫吸附法 (ELISA) 检测心肌损伤的血清标志物

包括肌酸激酶 (CK) 、乳酸脱氢酶 (LDH) 、肌钙蛋白T (cTnT) 、N末端脑钠肽前体 (NT-proBNP) 、可溶性ST2 (sST2) 和生长分化因子15 (GDF-15) ; 通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记测定法 (TUNEL) 和透射电子显微镜观察心肌细胞凋亡情况; 并分别通过Western Blot和实时定量聚合酶链反应 (qRT-PCR) 检测目的蛋白和mRNA的表达情况.

结果:

SMI不同剂量治疗可以降低大鼠心脏质量指数和左心室质量指数 (

0.05) 、显著提高左心室射血分数 (

0.05) ; 降低血清CK、LDH、cTnT和NT-proBNP水平 (

0.05 或

0.01) 、降低血清sST2和GDF-15水平 (

0.05或

0.01) ; 降低胶原体积分数、减少大鼠心肌Ⅰ型和Ⅲ型胶原蛋白的表达 (

0.05或

0.01)

有效缓解心肌纤维化; 研究发现SMI能够提高心肌中miR-30a和Bcl-2的表达水平

降低Bax的表达

抑制Caspase-3和Caspase-9的激活 (

0.05 或

0.01)

从而改善心肌细胞凋亡.

结论:

SMI可减轻DOX引起的心肌损伤和细胞凋亡

其机制可能是通过miR-30a促进心肌Bcl-2蛋白的靶向表达.

Abstract

Objective:

To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis.

Methods:

A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table

including the control group

the model group

miR-30a agomir group

SMI low-dose (SMI-L) group

and SMI high-dose (SMI-H) group

with 8 rats in each group. Except for the control group

the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury

and were given different regimens of continuous intervention for 2 weeks. Cardiac function was detected by echocardiography and myocardial pathological changes were observed by Van Gieson (VG) staining. Myocardial injury serum markers

including creatine kinase (CK)

lactate dehydrogenase (LDH)

troponin T (cTnT)

N-terminal pro-brain natriuretic peptide (NT-proBNP)

soluble ST2 (sST2)

and growth differentiation factor-15 (GDF-15) were detected by enzyme linked immunosorbent assay (ELISA). Cardiomyocyte apoptosis was observed by terminal deoxynucleotidyl transferase-mediated biotinylated dUTP triphosphate nick end labeling (TUNEL) and transmission electron microscopy

and the expressions of target proteins and mRNA were detected by Western blot and quantitative real time polymerase chain reaction (qRT-RCR)

respectively.

Results:

The treatment with different doses of SMI reduced rat heart mass index and left ventricular mass index (

0.05)

significantly improved the left ventricular ejection fraction (

0.05)

decreased the levels of serum CK

LDH

cTnT

and NT-proBNP (

0.05 or

0.01)

reduced the levels of serum sST2 and GDF-15 (

0.05 or

0.01)

decreased the collagen volume fraction

reduced the expressions of rat myocardial type Ⅰ and type Ⅲ collagen (

0.05 or

0.01)

and effectively alleviated myocardial fibrosis. And the study found that SMI promoted the expression levels of miR-30a and Bcl-2 in myocardium

and down-regulated the expression of Bax

which inhibited the activation of Caspase-3 and Caspase-9 (

0.05 or

0.01)

and improved myocardial cell apoptosis.

Conclusions:

SMI can alleviate myocardial injury and apoptosis caused by DOX

and its mechanism possibly by promoting the targeted expression of myocardial Bcl-2 protein through miR-30a.

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