The role of Drp1 mediated mitochondrial dynamics balance in sepsis induced cardiomyopathy
10.3760/cma.j.issn.1671-0282.2022.06.012
- VernacularTitle:Drp1介导的线粒体动力学平衡在脓毒症心肌细胞损伤的机制研究
- Author:
Chunxiao FU
1
;
Xiu YUAN
;
Han WANG
;
Shaojun LI
;
Liang ZHOU
;
Liping TAN
Author Information
1. 重庆医科大学附属儿童医院急诊科 儿童发育疾病研究教育部重点实验室 国家儿童健康与疾病临床医学研究中心 儿童发育重大疾病国家国际科技合作基地 儿科学重庆市重点实验室，重庆 400014
- Keywords:
Mitochondrial dynamics;
Sepsis induced cardiomyopathy;
Mitochondria;
Mitochondrial function;
H9C2;
Drp1;
Mfn2;
Opa1
- From:
Chinese Journal of Emergency Medicine
2022;31(6):767-772
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To analyze the effect of inhibiting excessive mitochondrial fission mediated by dynamic related protein 1 (Drp1) on the function of injured cells and mitochondria in the septic myocardium, and to explore the protective effect of maintaining mitochondrial dynamic balance in the pathogenesis of sepsis induced cardiomyopathy(SIC).Methods:Rat H9C2 cardiomyocytes were cultured and stimulated with lipopolysaccharide (LPS) to establish a model of SIC. Mitochondrial division inhibitor 1 (Mdivi-1) was given 30 min before LPS stimulation. They were divided into the control group, LPS stimulated group (LPS), Mdivi-1 control group (Mdivi-1), and LPS+Mdivi-1 intervention group (LPS+Mdivi-1). CCK-8 was used to detect the cell viability, and lactate dehydrogenase (LDH) was used to detect cellular damage. A MitoTracker probe was used to observe mitochondrial morphology by laser scanning confocal microscopy, JC-1 staining was used to detect mitochondrial membrane potential level, a DCFH-DA probe was used to detect total ROS level, and an AnnexinV-FITC/PI probe was used to detect the cell apoptosis ratio. The expression levels of mitochondrial fission protein Drp1 and fusion proteins Optic Atrophy 1(Opa1) and Mitofusin2 (Mfn2) were detected by real-time PCR and Western blot. One-way ANOVA was used to compare the differences between groups, and the LSD- t test was used for pairwise comparisons between groups. Results:Compared with the control group, cell viability, the average length of mitochondria and the mitochondrial membrane potential were decreased, and ROS production, the cell apoptosis rate and LDH were increased in the LPS group (all P<0.05). After Mdivi-1 intervention, compared with the LPS-stimulated group, the cell viability was increased, myocardial cell damage was reduced, the average length of mitochondria was prolonged, mitochondrial dysfunction was alleviated, and the cell apoptosis rate was inhibited in the LPS+Mdivi-1 group (all P<0.05). Conclusions:Mdivi-1 might inhibit mitochondrial fission mediated by Drp1, maintain mitochondrial dynamic balance, alleviate mitochondrial dysfunction and protect myocardial cells from LPS-induced injury.
