Curcumin simultaneously improves mitochondrial dynamics and myocardial cell bioenergy after sepsis via the SIRT1-DRP1/ PGC-1α pathway

作者全名：Hou, Dongyao; Liao, Haitang; Hao, Shuai; Liu, Ruixue; Huang, He; Duan, Chenyang

作者地址：[Hou, Dongyao; Liao, Haitang; Hao, Shuai; Liu, Ruixue; Huang, He; Duan, Chenyang] Chongqing Med Univ, Affiliated Hosp 2, Dept Anesthesiol, Chongqing 400010, Peoples R China; [Hou, Dongyao] Hubei Univ Med, Taihe Hosp, Dept Anesthesiol, Shiyan 442000, Peoples R China; [Liao, Haitang] Chongqing Hosp Tradit Chinese Med, Dept Intens Care Unit, Chongqing 400011, Peoples R China; [Hao, Shuai] Nanjing Univ, Jinling Hosp, Res Inst Gen Surg, Med Sch, Nanjing 210002, Peoples R China

通信作者：Huang, H; Duan, CY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Dept Anesthesiol, Chongqing 400010, Peoples R China.

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001222721400001

JCR分区：Q1

影响因子：3.4

年份：2024

卷号：10

期号：7

开始页：　

结束页：　

文献类型：Article

关键词：Cardiac dysfunction; Mitochondrial biogenesis; Oxidative stress; Inflammation

摘要：Septic cardiomyopathy (SCM) is associated with an imbalance in mitochondrial quality and high mortality rates, with no effective treatment developed to date. Curcumin provides antioxidant, anti-inflammatory, cardiovascular, and mitochondrial protection. However, curcumin has not been confirmed to improve cardiac dysfunction in sepsis. We hypothesized that curcumin can reduce abnormal inflammatory responses by improving mitochondrial function as a novel mechanism to improve SCM. To explore this hypothesis, we used an in vivo male C57BL/6 mouse sepsis model and an in vitro model of lipopolysaccharide-stimulated HL -1 cells. The effects of curcumin on sepsis-induced cardiac dysfunction, inflammatory responses, and mitochondrial quality of cardiac cells were observed using quantitative polymerase chain reaction, western blotting, echocardiography, and transmission electron microscopy. Curcumin activated sirtuin 1 (SIRT1); increased expression of the mitochondrial biogenesis-related genes Pgc1 alpha , Tfam , and Nrf2; reduced dynamin-related protein 1 translocation from the cytoplasm to mitochondria; and restored the mitochondrial morphology and function in cardiac cells. Accordingly, curcumin protected heart function after septic shock and alleviated the effects of SCM. SIRT1 knockdown reversed the protective effects of curcumin on mitochondria. Therefore, curcumin promotes mitochondrial biogenesis and inhibits mitochondrial fragmentation by activating SIRT1, thereby improving the mitochondrial quality and reducing oxidative stress in cardiomyocytes and sepsisinduced cardiac dysfunction. These findings provide new evidence supporting the use of curcumin to treat SCM.

基金机构：National Natural Science Foundation of China [82272252]; Chongqing Talents Program [CQYC202103061]; Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University

基金资助正文：<B>Funding</B> This work was supported by the National Natural Science Foundation of China [grant no. 82272252] , Chongqing Talents Program [grant no. CQYC202103061] , and Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University. The funders played no roles in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication.