线粒体自噬受体FUNDC1在脓毒症大鼠心肌损伤中对氧化应激响应的调控  

Regulation of mitochondrial autophagy receptor FUNDC1 in response to oxidative stress in sepsis myocardial injury

作　　者：佘丽萍 王垚[2] 黄敏 徐剑 邓晓静 周苏明 SHE Liping;WANG Yao;HUANG Min;XU Jian;DENG Xiaojing;ZHOU Suming(Department of Geriatric Intensive Care Medicine,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;Department of Cardiovascular Medicine,The First Affiliated Hospital of Nanjing Medical University,Nanjing 210029,China;Department of Critical Care Medicine,Geriatric Hospital,Nanjing Medical University,Nanjing 210036,China)

机构地区：[1]南京医科大学第一附属医院老年重症医学科,江苏南京210029 [2]南京医科大学第一附属医院心血管内科,江苏南京210029 [3]南京医科大学附属老年医院重症医学科,江苏南京210036

出　　处：《陕西医学杂志》2025年第4期441-446,共6页Shaanxi Medical Journal

基　　金：国家自然科学基金资助项目(2200387)。

摘　　要：目的:探讨线粒体自噬受体FUNDC1在脓毒症心肌损伤中的作用及其对氧化应激的影响。方法:选取大鼠心肌细胞H9C2,分为对照组(不做处理)、模型组(脓毒症模型)、FUNDC1过表达组和FUNDC1敲低组。通过细胞计数试剂盒8(CCK-8)、流式细胞术、三磷酸腺苷(ATP)检测、JC-1荧光染色、DCFH-DA荧光染色、酶活性检测、蛋白免疫印记(WB)、酶联免疫吸附(ELISA)方法检测各组细胞活力、凋亡率、线粒体功能、氧化应激水平、炎症反应、FUNDC1及相关蛋白表达。结果:与对照组比较,模型组、FUNDC1过表达组、FUNDC1敲低组心肌细胞活力、ATP含量、线粒体膜电位、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平、LC3-Ⅱ/LC3-Ⅰ比例及炎性因子水平均降低,模型组低于FUNDC1过表达组,FUNDC1敲低组低于模型组(均P<0.05),与对照组比较,模型组、FUNDC1过表达组、FUNDC1敲低组心肌细胞凋亡率、ROS水平、p62表达均升高,FUNDC1敲低组高于模型组,模型组高于FUNDC1过表达组(均P<0.05)。与对照组比较,模型组、FUNDC1敲低组心肌细胞FUNDC1表达均下降,FUNDC1过表达组升高(均P<0.05)。结论:线粒体自噬受体FUNDC1在脓毒症心肌损伤中发挥着重要的保护作用,其机制可能与调控线粒体自噬、减轻氧化应激和炎症反应有关,FUNDC1可能成为治疗脓毒症心肌损伤的新的潜在靶点。Objective:To investigate the role of mitochondrial autophagy receptor FUNDC1 in myocardial injury in sepsis and its effect on oxidative stress.Methods:Rat cardiomyocyte H9C2 cell line was selected and divided into control group(no treatment),model group(sepsis model),FUNDC1 overexpression group and FUNDC1 knockdown group.Cell viability,apoptosis rate,mitochondrial function,oxidative stress,inflammation and were detected by cell counting kit 8(CCK-8),flow cytometry,adenosine triphosphate(ATP),JC-1 fluorescence staining,DCFH-DA fluorescence staining,enzyme activity detection,protein immunoimprinting(WB),and enzyme-linked immunosorption(ELISA)Expression of FUNDC1 and related proteins.Results:Compared with the control group,myocardial cell viability,ATP content,mitochondrial membrane potential,SOD,CAT level,LC3-Ⅱ/LC3-Ⅰratio and inflammatory factor level in model group,FUNDC1 overexpression group and FUNDC1 knockdown group were all decreased,and the model group was lower than the FUNDC1 overexpression group.FUNDC1 knockdown group was lower than the model group(all P<0.05).Compared with the control group,the apoptosis rate,ROS level and p62 expression of cardiomyocytes in the model group,FUNDC1 overexpression group and FUNDC1 knockdown group were higher than the model group,and the model group was higher than the FUNDC1 overexpression group(all P<0.05).Compared with control group,FUNDC1 expression in cardiomyocytes of model group and FUNDC1 knockdown group was decreased,and FUNDC1 overexpression group was increased(all P<0.05).Conclusion:Mitochondrial autophagy receptor FUNDC1 plays an important protective role in myocardial injury in sepsis,and its mechanism may be related to regulating mitochondrial autophagy,alleviating oxidative stress and inflammatory response.FUNDC1 may be a new potential target for the treatment of myocardial injury in sepsis.

关 键 词：心肌细胞 线粒体自噬 FUNDC1 脓毒症 心肌损伤 氧化应激 

分 类 号：R542.2[医药卫生—心血管疾病]