Effects of succinate dehydrogenase inhibitor on succinate metabolism and inflammatory injury in myocardial tissue of endotoxemic rats

Bo QI; Xizhu ZHANG; Fei JIANG; He ZHANG; Jiajun CAI; Guozhi LI

doi:10.16016/j.1000-5404.202003125

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Effects of succinate dehydrogenase inhibitor on succinate metabolism and inflammatory injury in myocardial tissue of endotoxemic rats

更新时间：2026-01-09

- Effects of succinate dehydrogenase inhibitor on succinate metabolism and inflammatory injury in myocardial tissue of endotoxemic rats
- Journal of Third Military Medical University Vol. 42, Issue 19, Pages: 1938-1943(2020)
- 作者机构：
- 作者简介：
- 基金信息：
- DOI：10.16016/j.1000-5404.202003125
  CLC：
- Received：23 March 2020，
  
  Published：15 October 2020
- 稿件说明：
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Bo QI, Xizhu ZHANG, Fei JIANG, et al. Effects of succinate dehydrogenase inhibitor on succinate metabolism and inflammatory injury in myocardial tissue of endotoxemic rats[J]. Journal of Third Military Medical University, 2020, 42(19): 1938-1943.
DOI：

Bo QI, Xizhu ZHANG, Fei JIANG, et al. Effects of succinate dehydrogenase inhibitor on succinate metabolism and inflammatory injury in myocardial tissue of endotoxemic rats[J]. Journal of Third Military Medical University, 2020, 42(19): 1938-1943. DOI： 10.16016/j.1000-5404.202003125.

摘要

Abstract

Objective

To investigate the effects of succinate dehydrogenase (SDH) inhibitor on succinate metabolism and inflammatory injury in myocardial tissue of endotoxemic rats.

Methods

Forty specific pathogen free male Sprague-Dawley rats

weighing 200~220 g

were randomly divid

ed into 4 groups (

=10): saline treatment group (group C)

SDH inhibitor dimethyl malonate (DMM)+saline treatment group (group DC)

LPS treatment group (group E) and DMM+LPS treatment group (group DE). Lipopolysaccharide (LPS

20 mg/kg) was intraperitoneally injected to rats in group E and DE to establish the endotoxemia model. After LPS administration for 4 h

the rats in the group DC and DE were treated with DMM (160 mg/kg) through intraperitoneal injection. After DMM administration for 4 h

the serum level of cardiac troponin I (cTnI)

and the contents of TNF-α and IL-1β in myocardial tissue were detected with enzyme-linked immunosorbent assay. The myocardial succinate level was determined with a commercial succinate detection kit. The myocardial SDH expression was detected with Western blotting and immunofluorescence assay. The myocardial expression levels of hypoxia inducible factor-1α (HIF-1α)

phosphorylated inhibitor of NF-κB (p-IκB-α) and total IκB-α were determined with Western blotting.

Results

Compared with those in group C

the levels of cTnI

succinate

SDH

HIF-1α

p-IκB-α

TNF-α and IL-1β were significantly elevated in group E and group DE (

0.05). And the levels of cTnI

succinate

TNF-α

IL-1β

HIF-1α and p-IκB-αe were markedly decreased in the group DE than the group E (

0.05).

Conclusion

The myocardial contents of succinate and SDH are remarkably increased in endotoxemic rats. SDH inhibition with DMM can effectively attenuate the accumulation of succinate and subsequently alleviate the productions of TNF-α and IL-1β

which possibly through suppressing the NF-κB and HIF-1α pro-inflammatory pathway.

关键词

Keywords

references

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