昆明医科大学学报2025，Vol.46Issue(12)：58-68,11.DOI:10.12259/j.issn.2095-610X.S20251207
基于外泌体STAT3蛋白转运探讨干细胞在对梗死心脏修复及心电生理的影响
Effects of Stem Cells on Myocardial Infarction Repair and Cardiac Electrophysiology Based on Exosomal STAT3 Protein Transport
摘要
Abstract
Objective To investigate the role of bone marrow-derived mesenchymal stem cell(BMSCs)-derived exosomes(Exo)in transferring signal transduction and transcriptional activator 3(STAT3)protein in myocardial infarction(MI).Methods A rat MI model was established by ligation of the left anterior descending coronary artery.The animals were randomly divided into Sham,MI,and BMSCs-Exo groups.Additionally,Exo-pcDNA,Exo-pcDNA-STAT3,Exo-si-NC,and Exo-si-STAT3 groups were established to investigate the effects of upregulating or inhibiting STAT3 expression in Exo on cardiac function.At 2 and 4 weeks after surgery,rat electrocardiograms(ECG)and hemodynamic parameters were measured,including left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),maximum rate of pressure rise in left ventricle(+dp/dtmax),and maximum rate of pressure decline in left ventricle(-dp/dtmax).Western blot(WB)analysis was used to detect the expression levels of related proteins in myocardial tissue,including phosphorylated signal transducer and activator of transcription 3(p-STAT3),B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),and cleaved caspase-3(Cleaved-caspase-3).Results Compared with the MI group,the BMSCs-Exo group showed significant recovery of ST segment,QRS wave,and QT interval(F=23.462,P<0.001),and decreased arrhythmia incidence(χ2=7.248,P=0.009).Simultaneously,LVEDP decreased,and LVSP and±dp/dtmax improved(F=19.601,P<0.001).In the transfection groups,compared with the Exo-pcDNA group,the Exo-pcDNA-STAT3 group showed elevated S wave amplitude(P<0.05)and reduced arrhythmia incidence to 37.5%.Compared with the Exo-si-NC group,the Exo-si-STAT3 group showed prolonged QT interval,widened T wave,and decreased S wave amplitude(F=30.592,P<0.001),with arrhythmia rate increased to 87.5%.Cardiac function assessment showed that the Exo-pcDNA-STAT3 group had decreased LVEDP(F=14.937,P<0.001),while the Exo-si-STAT3 group showed elevated ASBP,LVSP,and+dp/dtmax(F=16.213,P<0.001),suggesting increased cardiac workload.WB results showed that the Exo-pcDNA-STAT3 group had upregulated p-STAT3 and Bcl-2 expression,while Bax and Cleaved-caspase-3 were downregulated(F=331.518,901.008,545.635,and 516.670,P<0.001);conversely,the Exo-si-STAT3 group showed opposite trends.Conclusion BM-SCs-derived exosomes improve cardiac function,reduce arrhythmias,and attenuate myocardial apoptosis after MI by delivering STAT3.Upregulation of STAT3 enhances the cardioprotective effects of exosomes,whereas STAT3 inhibition weakens these benefits.关键词
骨髓间充质干细胞/外泌体/传递信号转导和转录激活因子3/心肌梗死/心电生理Key words
Bone marrow mesenchymal stem cells/Exosomes/Signal transducer and activator of transcription 3/Myocardial infarction/Electrophysiology分类
医药卫生引用本文复制引用
SHEN Xiaoxia,FENG Chunhui,ZHAO Xiaodong..基于外泌体STAT3蛋白转运探讨干细胞在对梗死心脏修复及心电生理的影响[J].昆明医科大学学报,2025,46(12):58-68,11.基金项目
河北省医学科学研究基金(20242075) （20242075）
