[1]宋艳玲,陈明慧,刘皇军.内皮祖细胞微囊泡通过p38丝裂原活化蛋白激酶/核因子-κB通路保护心肌缺血再灌注损伤实验研究[J].陕西医学杂志,2026,(1):29-34.[doi:DOI:10.3969/j.issn.1000-7377.2026.01.005]
　SONG Yanling,CHEN Minghui,LIU Huangjun.Experimental study of endothelial progenitor cell-derived microvesicles protect myocardial ischemia-reperfusion injury through the p38 MAPK/NF-κB pathway[J].,2026,(1):29-34.[doi:DOI:10.3969/j.issn.1000-7377.2026.01.005]
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内皮祖细胞微囊泡通过p38丝裂原活化蛋白激酶/核因子-κB通路保护心肌缺血再灌注损伤实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年1期
页码:
29-34
栏目:
基础研究
出版日期:
2026-01-05

文章信息/Info

Title:
Experimental study of endothelial progenitor cell-derived microvesicles protect myocardial ischemia-reperfusion injury through the p38 MAPK/NF-κB pathway
作者:
宋艳玲1; 陈明慧2; 刘皇军1
（1.长江大学附属第一医院，湖北 荆州 434000；2.海南医科大学第一附属医院，海南 海口570100）
Author(s):
SONG Yanling1; CHEN Minghui2; LIU Huangjun1
（ 1.The First Affiliated Hospital of Yangtze University,Jingzhou 434000，China；2.The First Affiliated Hospital of Hainan Medical University ,Haikou 570100，China）
关键词:
心肌缺血再灌注损伤; 内皮祖细胞微囊泡; 细胞通路; 炎症; 心肌保护; 信号转导
Keywords:
Myocardial ischemia-reperfusion injury; Endothelial progenitor cell microvesicles; Cellular pathways; Inflammation; Cardioprotection; Signal transduction
分类号:
R 541.4
DOI:
DOI:10.3969/j.issn.1000-7377.2026.01.005
文献标志码:
A
摘要:
目的：探究内皮祖细胞微囊泡（EPC-MVs）对心肌缺血再灌注损伤（MIRI）的保护作用。方法：采用密度梯度离心法以及差数贴壁法分离和培养内皮祖细胞(EPCs)，收集EPCs并离心获取微囊泡（MVs）。大鼠分为假手术组、MIRI组、EPC-MVs组，每组3只。采用超声心动图检测大鼠心功能；ELISA检测心肌乳酸脱氢酶（LDH）、肌酸激酶同工酶-MB（CK-MB）、心肌肌钙蛋白I（cTnI）水平及肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）水平；HE染色观察心肌组织病理情况；Western blot检测心肌组织p38丝裂原活化蛋白激酶（p38 MAPK）和核因子-κB（NF-κB）表达水平。结果：EPC-MVs组较MIRI组左心室收缩末期内径（LVESD）、左心室舒张末期内径（LVEDD）显著降低，左心室射血分数（EF）、短轴缩短分数（FS）显著升高（均P<0.05）；EPC-MVs组大鼠血清LDH、CK-MB、cTnI水平显著降低(均P <0.05)。EPC-MVs组大鼠心肌纤维排列较整齐，肌纤维断裂较MIRI组减少，细胞间有较少的炎性细胞浸润。MIRI组大鼠炎症因子水平（IL-1β、TNF-α）、p-p38 MAPK、p-NF-κB水平显著升高（均P<0.01）；与MIRI组比较，EPC-MVs组大鼠炎症因子水平、p-p38 MAPK、p-NF-κB水平显著降低（均P<0.01）。结论：EPC-MVs对MIRI大鼠具有保护作用，其机制可能通过影响p38 MAPK/NF-κB信号通路进而影响炎症反应。
Abstract:
Objective:To investigate the cardioprotective effects of endothelial progenitor cell-derived microvesicles (EPC-MVs) against myocardial ischemia-reperfusion injury (MIRI).Methods：Endothelial progenitor cells (EPCs) were isolated and cultured using density gradient centrifugation combined with differential adhesion methods.EPC-MVs were collected via ultracentrifugation.Sprague-Dawley rats were randomized into three groups (n=3 per group):sham-operated,MIRI,and EPC-MVs-treated.Cardiac function was assessed by transthoracic echocardiography to measure left ventricular end-systolic diameter (LVESD),end-diastolic diameter (LVEDD),ejection fraction (EF),and fractional shortening (FS).Serum levels of lactate dehydrogenase (LDH),creatine kinase-MB (CK-MB),cardiac troponin I (cTnI),tumor necrosis factor-α (TNF-α),and interleukin-1β (IL-1β) were quantified by enzyme-linked immunosorbent assay (ELISA).Histopathological alterations in myocardial tissue were evaluated via hematoxylin-eosin (HE) staining.Protein expression levels of phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and nuclear factor-kappa B (p-NF-κB) were analyzed by Western blot.Results:Compared to the MIRI group,the EPC-MVs group exhibited significantly reduced LVESD and LVEDD (all P<0.05),accompanied by increased EF and FS (all P<0.05).Serum biomarkers of myocardial injury (LDH,CK-MB,cTnI) and pro-inflammatory cytokines (TNF-α,IL-1β) were markedly attenuated in the EPC-MVs group (all P<0.05).Histopathological analysis revealed improved myocardial architecture in the EPC-MVs group,characterized by alleviated myofibril disarray,reduced interstitial inflammatory cell infiltration,and diminished necrosis compared to the MIRI group.Western blot demonstrated that EPC-MVs treatment significantly suppressed MIRI-induced activation of p-p38 MAPK and p-NF-κB (all P<0.01).Conclusion:EPC-MVs confer cardioprotection against MIRI,potentially through inhibition of the p38 MAPK/NF-κB signaling pathway,thereby attenuating inflammatory cascades.

参考文献/References:

[1]国家心血管病中心.中国心血管健康与疾病报告[M].北京：中国协和医科大学出版社，2023:28-30.
[2]赵明慧,薛凌.毛蕊异黄酮靶向高迁移率族蛋白1对心肌缺血再灌注损伤大鼠保护作用实验研究[J].陕西医学杂志,2024,53(7):873-878,883.
[3]SNCHEZ C D,TORRES L A,GONZLEZ A,et al.Ischemia/reperfusion injury:Pathophysiology,current clinical management,and potential preventive approaches[J].Mediators of Inflammation,2020,1:840-845.
[4]HERNANDEZ S,CHINDA K,ONG S B,et al.The role of redox dysregulation in the inflammatory response to acute myocardial ischaemia-reperfusion injury-adding fuel to the fire[J].Current Medicinal Chemistry,2018,25(11):1275-1293.
[5]吴青芸,苏强.抗氧化纳米药物介导心肌缺血再灌注损伤的靶向治疗[J].中国组织工程研究,2025,29(34):7431-7438.
[6]刘琳,谢丹,赵博,等.七氟烷抑制L型钙离子通道调控MAPK/ERK信号通路改善大鼠心肌缺血再灌注损伤[J].解剖科学进展,2023,29(1):85-88.
[7]ALEXANDRU N,ANDREI E,SAFCIUC F,et al.Intravenous administration of allogenic cell-derived microvesicles of healthy origins defend against atherosclerotic cardiovascular disease development by a direct action on endothelial progenitor cells[J].Cells,2020,9(2):423-425.
[8]CHEN C W,WANG L L,ZAMAN S,et al.Sustained release of endothelial progenitor cell-derived extracellular vesicles from shear-thinning hydrogels improves angiogenesis and promotes function after myocardial infarction[J].Cardiovascular Research,2018,114(7):1029-1040.
[9]MARTNEZ-LIMN A,JOAQUIN M,CABALLERO M,et al.The p38 pathway:From biology to cancer therapy[J].International Journal of Molecular Sciences,2020,21(6):1913-1914.
[10]WANG J,LIU Y,GUO Y,et al.Function and inhibition of P38 MAP kinase signaling:Targeting multiple inflammation diseases[J].Biochemical Pharmacology,2024,220(1):115-119.
[11]蓝艳梅,陆正峰,毛德文,等.解毒化瘀颗粒对肝衰竭大鼠miR-146a-5p/NF-κB途径及肠道菌群的干预效应研究[J].时珍国医国药,2024,35(15):3305-3314.
[12]JIANG L,YANG A,LI X,et al.Down-regulation of VCAM-1 in bone mesenchymal stem cells reduces inflammatory responses and apoptosis to improve cardiac function in rat with myocardial infarction[J].International Immunopharmacology,2021,101(1):108-180.
[13]XU J,BAI S,CAO Y,et al.miRNA-221-3p in endothelial progenitor cell-derived exosomes accelerates skin wound healing in diabetic mice[J].Diabetes,Metabolic Syndrome and Obesity:Targets and Therapy,2020,13(1):1259-1270.
[14]LI L,LI X,ZHANG Z,et al.Effects of hydrogen-rich water on the PI3K/AKT signaling pathway in rats with myocardial ischemia-reperfusion injury[J].Current Molecular Medicine,2020,20(5):396-406.
[15]林芸芸,黄珊,宋艳玲,等.阿托伐他汀诱导EPC-MVs增多对STEMI患者心肌细胞的保护作用研究[J].中国药房,2019,30(10):1396-1402.
[16]郑力榕,包阿如汗,张瑞芬,等.心肌缺血再灌注损伤机制及药物治疗研究进展[J].中国临床研究,2023,36(10):1580-1584.
[17]白雪.常规超声心动图对经皮冠状动脉介入术后心肌缺血再灌注损伤的应用效果[J].影像研究与医学应用,2021,5(17):28-29.
[18]石春龙,杨力强,农复香,等.中医药调控间充质干细胞治疗心肌缺血再灌注损伤的研究进展[J].辽宁中医杂志,2024,51(6):206-211.
[19]HASSANPOUR M,SALYBKOV A A,KOBAYASHI S,et al.Anti-inflammatory prowess of endothelial progenitor cells in the realm of biology and medicine[J].Npj Regenerative Medicine,2024,9(1):1-15.
[20]田俊斌,赵静,罗斌,等.重楼皂苷Ⅰ预防给药对心肌缺血再灌注损伤大鼠调节PI3K/AKT信号通路的作用研究[J].西部医学,2024,36(3):317-324.
[21]熊岳,李铁成.黄角颗粒预处理对大鼠心肌缺血再灌注损伤的保护机制[J].中西医结合心脑血管病杂志,2021,19(23):4062-4065.
[22]GEORGE A L,BANGALORE-PRAKASH P,RAJORIA S,et al.Endothelial progenitor cell biology in disease and tissue regeneration[J].Journal of Hematology & Oncology,2011,4(1):24-26.
[23]ROMERO-BECERRA R,SANTAMANS A M,FOLGUEIRA C,et al.p38 MAPK pathway in the heart:New insights in health and disease[J].International Journal of Molecular Sciences,2020,21(19):7412-7418.
[24]黎义炬,吉登军.基于NF-κB信号通路探讨中药复方治疗急性肺损伤的研究进展[J].湖南中医杂志,2025,41(1):171-174.
[25]BARNABEI L,LAPLANTINE E,MBONGO W,et al.NF-κB:At the borders of autoimmunity and inflammation[J].Frontiers in Immunology,2021,12(1):716-719.

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备注/Memo

备注/Memo:
海南省自然科学基金资助项目（823RC577）
更新日期/Last Update: 2026-01-05