Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice

Weixiang MIN; Xuejun CHEN; Dexiang MA; Yu LIU; Shuting LIU; Mengxi SHI

doi:10.16016/j.2097-0927.202205103

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Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice

Basic Medicine | 更新时间：2026-01-09

- Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice
- Journal of Army Medical University Vol. 44, Issue 22, Pages: 2285-2290(2022)
- 作者机构：
  
  610072 成都, 四川省医学科学院 · 四川省人民医院麻醉科
- 作者简介：
- 基金信息：
  
  the Research Fund of Sichuan Academy of Medical Sciences · Sichuan Provincial People's Hospital(30305020225)
- DOI：10.16016/j.2097-0927.202205103
  CLC： R542.2;R631.2;R914.4
- Received：19 May 2022，
  
  Revised：2022-08-02，
  
  Published：30 November 2022
- 稿件说明：
移动端阅览
Weixiang MIN, Xuejun CHEN, Dexiang MA, et al. Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice[J]. Journal of Army Medical University, 2022, 44(22): 2285-2290.
DOI：

Weixiang MIN, Xuejun CHEN, Dexiang MA, et al. Effect and mechanism of dimethyl fumarate on septic cardiomyopathy in mice[J]. Journal of Army Medical University, 2022, 44(22): 2285-2290. DOI： 10.16016/j.2097-0927.202205103.

摘要

目的

探讨富马酸二甲酯(dimethyl fumarate，DMF)对小鼠脓毒症心肌病的作用及其机制。

方法

选取30只8~10周龄的C57/BL6J雄性小鼠(22~24 g)随机分为空白组、模型组、治疗组(每组10只)。治疗组连续7天灌胃DMF(25 mg/kg)，每天一次；另两组灌胃等量生理盐水。第七天给药结束后1 h，模型组和治疗组取一半小鼠腹腔注射大剂量(30 mg/kg)脂多糖(lipopolysaccharide

LPS)，空白组取一半小鼠给予等量生理盐水，观察72 h内的生存率。剩余模型组和治疗组小鼠给予LPS(15 mg/kg)，空白组则给予等量生理盐水。采用经胸心脏超声评估24 h心功能，处死小鼠后留取心脏及血浆。采用生化仪检测血浆肌酸激酶同工酶(creatine kinase isoenzymes，CK-MB)和乳酸脱氢酶(lactic dehydrogenase，LDH)水平；HE染色观察心肌结构；采用比色法检测心肌氧化应激损伤标志物丙二醛(malondialdehyde，MDA)、还原型谷胱甘肽(glutathione，GSH)、氧化型谷胱甘肽(oxidized glutathione，GSSG)含量及超氧化物歧化酶(superoxide dismutase，SOD)活性；Western blot检测心肌核转录因子E2相关因子2(nuclear factor E2-related factor 2，Nrf2)及下游靶基因的蛋白水平。

结果

模型组小鼠72 h生存率仅20%，而治疗

组小鼠有80%。相比空白组，模型组血浆CK-MB和LDH含量均上升，小鼠心肌细胞出现水肿

排列紊乱。模型组左室射血分数(left ventricular ejection fraction，LVEF)和左室短轴缩短率(left ventricular fractional shortening，LVFS)均下降(

0.01)；MDA和GSSG含量明显增加，GSH减少且SOD活性降低(

0.01)；Nrf2、血红素加氧酶1(heme oxygenase，HO-1)及SOD2蛋白表达下降(

0.01)。相比模型组，治疗组小鼠心肌损伤标志物水平降低，心功能有所恢复，心肌结构破坏较轻，氧化应激改善，Nrf2及下游靶蛋白表达均有所增强(

0.01)。

结论

DMF可以激活Nrf2抗氧化通路，提高心脏的抗氧化应激能力，对小鼠脓毒症心肌病起到保护作用。

Abstract

Objective

To investigate the effect and mechanism of dimethyl fumarate (DMF) on septic cardiomyopathy in mice.

Methods

Thirty C57/BL6J male mice (22~24 g) aged 8~10 weeks were randomly divided into the blank group

the model group and the treatment group (10 mice in each group). The treatment group had been given intragastric administration of DMF (25 mg/kg) once a day for 7 d

and the other 2 groups were given a gavage of an equal volume of saline. In 1 h after the last time of intragastric administration

half of the mice in the model group and the treatment group were intraperitoneally injected with high-dose (30 mg/kg) lipopolysaccharide (LPS)

and half of the mice in the blank group were given an equal volume of saline to observe the survival rate within 72 h. The remaining mice in the model group and treatment group were intraperitoneally injected with LPS (15 mg/kg) and the blank group was given an equal volume of saline. Transthoracic echocardiography was used to evaluate cardiac function within 24 h. The animals were sacrificed and heart and plasma was collected. The levels of CK-MB and LDH in plasma were detected by biochemical analyzer; HE staining was used to observe the myocardial structure; the contents of MDA

GSH and GSSG and the activity of SOD in heart tissues were detected using colorimetric assay; the protein levels of Nrf2 and its downstream target genes in heart were detected by Western blotting.

Results

The 72 h survival rate of the model group mice was only 20%

while that of the treatment group mice was 80%. Compared with the blank group

the levels of CM-MB and LDH of plasma in the model group increased

and cardiac myocytes were swelling and disordered. LVEF% and FS% both reduced (

0.01); the contents of MDA and GSSG surged

but GSH and SOD activity decreased (

0.01); the protein levels of Nrf2

HO-1 and SOD2 dropped (

0.01). Compared with the model group

the treatment group showed lower levels of myocardial injury markers

improved cardiac function

less damaged myocardial structure and reduced oxidative stress injury

and the protein expression of Nrf2 and its downstream target gene also enhanced (

0.01).

Conclusion

DMF can activate the antioxidant pathway of Nrf2

improve the ability of heart to resist oxidative stress

and play a protective role in septic cardiomyopathy in mice.

关键词

Keywords

references

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