超声靶向微泡破坏协同骨髓间充质干细胞外泌体递送微小RNA-98-5p对急性心肌梗死模型大鼠的治疗作用  

Therapeutic effects of ultrasound-targeted microbubble destruction combined with bone marrow mesenchymal stem cells-derived exosomes delivering microRNA-98-5p in a rat model of acute myocardial infarction

作　　者：徐海飞[1] 张伟[2] 罗伟俊[2] 雷建明[1] XU Haifei;ZHANG Wei;LUO Weijun;LEI Jianming(Department of Ultrasound,Lishui People's Hospital,Lishui,Zhejiang 323000,China;Department of Cardiology,Lishui People's Hospital,Lishui,Zhejiang 323000,China)

机构地区：[1]浙江省丽水市人民医院超声科,丽水323000 [2]浙江省丽水市人民医院心血管内科,丽水323000

出　　处：《浙江中西医结合杂志》2025年第4期318-323,共6页Zhejiang Journal of Integrated Traditional Chinese and Western Medicine

基　　金：丽水市科技计划项目(No.2021GYX20)。

摘　　要：目的探究超声靶向微泡破坏(UTMD)协同骨髓间充质干细胞(BMSCs)外泌体(EXO)递送微小RNA(miR)-98-5p对急性心肌梗死(AMI)模型大鼠的治疗作用。方法42只SD大鼠随机分为假手术(sham)组、AMI组、AMI+EXO组、AMI+miR-98-5p模拟物阴性对照(mimic NC)-EXO组、AMI+miR-98-5p模拟物(mimic)-EXO组、AMI+UTMD组、AMI+miR-98-5p mimic-EXO+UTMD组,每组6只。采用结扎左冠状动脉前降支的方法建立AMI模型。实时荧光定量聚合酶链式反应(qRT-PCR)检测大鼠心肌组织miR-98-5p表达,原位末端转移酶标记(TUNEL)法检测大鼠心肌组织细胞凋亡程度,酶联免疫吸附试验(ELISA)检测大鼠血清心肌肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)和乳酸脱氢酶(LDH)水平。结果与sham组比较,AMI组大鼠心肌组织中miR-98-5p低表达,血清cTnT、CK-MB、LDH水平升高(P<0.01),心肌组织出现明显的细胞凋亡。与AMI+mimic NC-EXO组比较,AMI+miR-98-5p mimic-EXO组大鼠心肌组织miR-98-5p[(1.46±0.56)比(0.63±0.48),P<0.01]高表达,血清cTnT[(89.11±9.17)U/mL比(166.58±11.34)U/mL,P<0.01]、CK-MB[(416.22±15.19)U/L比(554.12±15.86)U/L,P<0.01]和LDH[(571.00±19.78)U/L比(686.03±4.81)U/L,P<0.01]水平降低,心肌组织细胞凋亡改善。与AMI+miR-98-5p mimic-EXO组比较,AMI+miR-98-5p mimic-EXO+UTMD组大鼠心肌组织miR-98-5p[(2.76±0.95)比(1.46±0.56),P<0.01]高表达,血清cTnT[(45.69±5.46)U/mL比(89.11±9.17)U/mL,P<0.01]、CK-MB[(281.86±7.26)U/L比(416.22±15.19)U/L,P<0.01]和LDH[(463.49±15.75)U/L比(571.00±19.78)U/L,P<0.01]水平降低,心肌组织细胞凋亡程度明显改善。结论UTMD协同BMSCs EXO递送miR-98-5p对AMI模型大鼠具有治疗作用。Objective To investigate the therapeutic effects of ultrasound-targeted microbubble destruction(UTMD)combined with bone marrow mesenchymal stem cells(BMSCs)-derived exosomes(EXO)delivering microRNA-98-5p(miR-98-5p)in a rat model of acute myocardial infarction(AMI).Methods Forty-two Sprague-Dawley rats were randomly divided into seven groups:sham-operated(sham)group,AMI group,AMI+EXO group,AMI+miR-98-5p mimic negative control(mimic NC)-EXO group,AMI+miR-98-5p mimic-EXO group,AMI+UTMD group,and AMI+miR-98-5p mimic-EXO+UTMD group,with 6 rats in each group.The AMI model was established by ligating the left anterior descending coronary artery.The expression of miR-98-5p in myocardial tissue was detected using quantitative real-time polymerase chain reaction.The apoptosis in myocardial tissue was assessed using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling.The serum levels of cardiac troponin T(cTnT),creatine kinase isoenzyme(CK-MB),and lactate dehydrogenase(LDH)were measured using enzyme-linked immunosorbent assay.Results Compared with the sham group,the AMI group exhibited lower miR-98-5p expression in myocardial tissue and elevated serum levels of cTnT,CK-MB,and LDH(P<0.01),as well as significant myocardial apoptosis.Compared with the AMI+mimic NC-EXO group,the AMI+miR-98-5p mimic-EXO group showed significantly higher miR-98-5p expression in myocardial tissue[(1.46±0.56)vs.(0.63±0.48),P<0.01],and decreased serum levels of cTnT[(89.11±9.17)U/mL vs.(166.58±11.34)U/mL,P<0.01],CK-MB[(416.22±15.19)U/L vs.(554.12±15.86)U/L,P<0.01],and LDH[(571.00±19.78)U/L vs.(686.03±4.81)U/L,P<0.01],as well as improved myocardial apoptosis.Compared with the AMI+miR-98-5p mimic-EXO group,the AMI+miR-98-5p mimic-EXO+UTMD group showed significantly higher miR-98-5p expression in myocardial tissue[(2.76±0.95)vs.(1.46±0.56),P<0.01],and decreased serum levels of cTnT[(45.69±5.46)U/mL vs.(89.11±9.17)U/mL,P<0.01],CK-MB[(281.86±7.26)U/L vs.(416.22±15.19)U/L,P<0.01],and LDH[(463.49±15.75)U/L vs.(571.00±19.78

关 键 词：大鼠 急性心肌梗死 骨髓间充质干细胞外泌体 微小RNA-98-5p 超声靶向微泡破坏 

分 类 号：R541.4[医药卫生—心血管疾病]