广州医药2025，Vol.56Issue(9)：1201-1207,1237,8.DOI:10.20223/j.cnki.1000-8535.2025.09.006
抗增殖蛋白2对脓毒症心肌损伤线粒体功能稳态的作用机制研究
Research on the mechanism of prohibitin 2 on mitochondrial functional homeostasis in sepsis-induced myocardial injury
摘要
Abstract
Objective To explore the regulatory mechanism of septic myocardial injury by prohibitin 2(PHB2).Methods Rat myocardial cell lines(H9C2)were cultured in vitro and divided into control group,LPS group,LPS+PHB2 siRNA(si-PHB2)group.The indicators for detecting oxidative stress include the levels of intracellular malondialdehyde(MDA)and reactive oxygen species(ROS).The indicators for mitochondrial detection include adenosine triphosphate(ATP)levels,mitochondrial membrane potential,mitochondrial electron microscopy,and semi-quantitative mitochondrial scoring.Western blotting was used to detect the expression of PHB2,PTEN induced putative kinase(PINK1),Parkin,mitochondrial transcription factor A(TFAM).Results After LPS stimulation,MDA level and intracellular ROS level increased,ATP level decreased.Compared with LPS group,MDA(6.21±0.39 vs 3.59±0.33,P＜0.05)level and intracellular ROS level(15 131.37±88.72 vs 8 628.67±71.95,P＜0.05)in LPS+si-PHB2 group increased significantly,while ATP(3.46±0.34 vs 4.52±0.25,P＜0.05)and MMP(0.33±0.04vs0.55±0.09,P＜0.05)level further decreased.Compared with the normal group,the structure of mitochondria in LPS group and LPS+si-PHB2 group was damaged in different degree.The semi-quantitative score of mitochondrial damage showed that the damage in LPS+si-PHB2 group was more obvious than that in LPS group(1.42±0.10 vs 0.81±0.04,P＜0.05).Western blotting showed that the expression of PHB2,PINK1 and Parkin were up-regulated and the expression of TFAM was down-regulated after LPS treatment,mitohagy-related proteins PINK1(1.33±0.06 vs 1.79±0.21,P＜0.05),Parkin(1.43±0.08 vs 1.86±0.09,P＜0.05)and mitochondrial biogenetic protein TFAM(0.29±0.01 vs 0.74±0.06,P＜0.05)in LPS+si-PHB2 group were lower than those in LPS group.Conclusions LPS can promote the expression of PHB2 in rat cardiomyocytes.After interfering with PHB2 expression,we found that mitochondrial autophagy and biogenesis are inhibited,and mitochondrial dysfunction,oxidative stress exacerbated,suggesting that the up-regulation of PHB2 expression may restore mitochondrial homeostasis and improve mitochondrial function in septic myocardial injury.关键词
脓毒症/心肌损伤/线粒体/抗增殖蛋白2Key words
sepsis/myocardial injury/mitochondria/prohibitin 2引用本文复制引用
陈志江,曾成,赵纬,韦秋菊,单文琪,王惠丽..抗增殖蛋白2对脓毒症心肌损伤线粒体功能稳态的作用机制研究[J].广州医药,2025,56(9):1201-1207,1237,8.基金项目
广州市科技计划项目(2023A04J2434) （2023A04J2434）
