Yangxin Dawayimicol Honey Ointment Improves Cardiac Function in Rats by Regulating VDAC1/NLRP3/Bax/Bcl-2 Pathway

MA Jingzhuo; YAO Bo; CHEN Hengwen; HE Xuanhui

doi:10.13422/j.cnki.syfjx.20250321

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Yangxin Dawayimicol Honey Ointment Improves Cardiac Function in Rats by Regulating VDAC1/NLRP3/Bax/Bcl-2 Pathway

更新时间：2025-03-20

- Yangxin Dawayimicol Honey Ointment Improves Cardiac Function in Rats by Regulating VDAC1/NLRP3/Bax/Bcl-2 Pathway
  增强出版
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 31, Issue 8, Pages: 115-124(2025)
- 作者机构：
  
  1.中国中医科学院广安门医院，北京 100053
  2.长春中医药大学药学院，长春 130117
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20250321
  CLC： R256;R285.5;R825.4
- Received：10 September 2024，
  
  Accepted：20 November 2024，
  
  Online First：18 December 2024，
  
  Published：20 April 2025
- 稿件说明：
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马静卓,姚博,陈恒文等.养心达瓦依米西克蜜膏通过调节VDAC1/NLRP3/Bax/Bcl-2通路改善大鼠心功能[J].中国实验方剂学杂志,2025,31(08):115-124.

MA Jingzhuo,YAO Bo,CHEN Hengwen,et al.Yangxin Dawayimicol Honey Ointment Improves Cardiac Function in Rats by Regulating VDAC1/NLRP3/Bax/Bcl-2 Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(08):115-124.
马静卓,姚博,陈恒文等.养心达瓦依米西克蜜膏通过调节VDAC1/NLRP3/Bax/Bcl-2通路改善大鼠心功能[J].中国实验方剂学杂志,2025,31(08):115-124. DOI： 10.13422/j.cnki.syfjx.20250321.

MA Jingzhuo,YAO Bo,CHEN Hengwen,et al.Yangxin Dawayimicol Honey Ointment Improves Cardiac Function in Rats by Regulating VDAC1/NLRP3/Bax/Bcl-2 Pathway[J].Chinese Journal of Experimental Traditional Medical Formulae,2025,31(08):115-124. DOI： 10.13422/j.cnki.syfjx.20250321.

摘要

目的

探析养心达瓦依米西克蜜膏（YXDW）改善心肌梗死后大鼠心功能的作用及机制。

方法

将大鼠分为假手术组、模型组、福辛普利钠片组及YXDW低、中、高剂量组。该实验采用左前降支结扎构建大鼠心梗模型，YXDW组以0.27、0.54、1.08 g·kg

-1

·d

-1

剂量灌胃，福辛普利钠片组以3.60 mg·kg

-1

·d

-1

剂量灌胃，假手术组及模型组以等量0.5%羧甲基纤维素钠水溶液灌胃处理，连续灌胃4周，观察YXDW对大鼠体征、心脏指数的影响，超声心动图观察心功能变化，病理学检查评价心脏形态变化，酶联免疫吸附测定法（ELISA）评价白细胞介素-1

（IL-1

）、IL-6、氨基末端脑钠肽前体（NT-proBNP）、肿瘤坏死因子-

（TNF-

）等细胞炎症因子的变化，分别采用实时荧光定量聚合酶链反应（Real-time PCR）和蛋白免疫印迹法（Western blot）检测电压依赖性阴离子选择性通道蛋白1（VDAC1）、NOD样受体热蛋白结构域相关蛋白3（NLRP3）、线粒体凋亡相关基因B细胞淋巴瘤-2 （Bcl-2）、Bcl-2相关X蛋白（Bax）表达情况。

结果

YXDW各组大鼠生存状态普遍有所改善。超声心动图结果显示，与假手术组比较，模型组大鼠心脏左心室射血分数（LVEF）、左室短轴缩短率（LVFS）均显著下降（

0.01）；与模型组比较，各治疗组大鼠LVEF、LVFS均有不同程度增高（

0.01）。病理学检查显示，与模型组比较，各给药组大鼠心肌细胞变性减少，炎性浸润减轻，肌丝较完整，走形规则，心肌纤维明显减少。电镜结果显示，与模型组比较，YXDW各剂量组心肌细胞线粒体超微结构清楚，膜较完整，嵴较为致密，基质清楚，肌丝及闰盘排列较为规则。ELISA结果显示，与假手术组比较，模型组大鼠血清中IL-6、IL-1

、TNF-

均显著增高（

0.01）；与模型组比较，各给药组大鼠血清中IL-6、IL-1

、TNF-

均显著降低（

0.01）。与假手术组比较，模型组大鼠血清中NT-proBNP显著升高（

0.01）；与模型组比较，各给药组NT-proBNP显著降低（

0.01）。Real-time PCR、Western blot结果显示，与假手术组比较，模型组VDAC1、NLRP3、Bax/Bcl-2含量均明显升高（

0.05）；与模型组比较，各给药组VDAC1、NLRP3、Bax/Bcl-2含量均明显下降（

0.05）。

结论

养心达瓦依米西克蜜膏能够明显改善心肌梗死后大鼠心功能，其作用机制可能通过VDAC1/NLRP3/Bax/Bcl-2通路改善线粒体结构和功能，抑制炎症反应，从而改善心功能。

Abstract

Objective

To investigate the effect and mechanism of Yangxin Dawayimicol honey ointment （YXDW） in improving cardiac function in rats after myocardial infarction.

Methods

Rats were divided into the sham group， model group， fosinopril sodium tablet group， and YXDW low， medium， and high-dose groups. A rat myocardial infarction model was established by left anterior descending branch ligation. The YXDW groups were administered doses of 0.27， 0.54， and 1.08 g·kg

-1

·d

-1

， while the fosinopril sodium tablet group was given 3.60 mg·kg

-1

·d

-1

. The sham group and model group were treated with an equal amount of 0.5% sodium carboxymethyl cellulose solution. After continuous gavage for 4 weeks， the effects of YXDW on the signs and cardiac indices of the rats were observed. Echocardiography was used to assess cardiac function， and pathological examination was used to evaluate heart morphology. Enzyme-linked immunosorbent assay （ELISA） was used to assess changes in interleukin-1

（IL-1

）， IL-6， N-terminal pro-brain natriuretic peptide （NT-proBNP）， and tumor necrosis factor-

（TNF-

）. The expression of voltage-dependent anion-selective channel protein 1 （VDAC1）， nucleotide binding oligomerization domain-like receptor family pyrin domain-containing 3 （NLRP3）， B-cell lymphoma -2 （Bcl-2）， and Bcl-2-associated X protein （Bax） was detected by reverse transcription-polymerase chain reaction （Real-time PCR） and Western blot.

Results

The survival status of rats in all YXDW groups was generally improved. Echocardiographic results showed that， compared to the sham group， the model group exhibited a significant decrease in left ventricular ejection fraction （LVEF） and left ventricular short axis shortening rate （LVFS）， with statistical significance （

0.01）. Compared to the model group， rats in the treatment groups showed varying degrees of improvement in LVEF and LVFS， with statistical significance （

0.01）. Pathological examination revealed reduced myocardial cell degeneration， less inflammatory infiltration， intact myofilaments， regular shape， and significantly fewer myocardial fiber disruptions in the treatment groups compared to the model group. Electron microscopy results showed that， compared to the model group， the mitochondria of myocardial cells in the YXDW groups had clear ultrastructure， intact membranes， denser cristae， a clear matrix， and regular arrangement of myofilaments and intercalated discs. ELISA results showed that， compared to the sham group， serum levels of IL-6， IL-1

， and TNF

-α

were significantly higher in the model group， with statistical significance （

0.01）. However， in the treatment groups， the serum levels of IL-6， IL-1

， and TNF-

were significantly reduced， with statistical significance （

0.01）. NT-proBNP levels were signi

ficantly higher in the model group compared to the sham group （

0.01）， but significantly lower in the treatment groups （

0.01）. Furthermore， Real-time PCR and Western blot results showed that compared to the sham group， the levels of VDAC1， NLRP3， and Bax/Bcl-2 were significantly higher in the model group （

0.05）. In the treatment groups， these levels were significantly lower than the model group （

0.05）.

Conclusion

YXDW significantly improved cardiac function in rats after myocardial infarction. Its mechanism of action may involve the VDAC1/NLRP3/Bax/Bcl-2 pathway to improve mitochondrial structure and function and inhibit the inflammatory response， thereby improving cardiac function.

关键词

Keywords

references

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