实用医学杂志2025，Vol.41Issue(22)：3510-3519,10.DOI:10.3969/j.issn.1006-5725.2025.22.007
分泌型磷蛋白1、髓样分化因子88在二乙酰吗啡致心肌细胞凋亡中的作用
Role of SPP1 and MYD88 in diacetylmorphine-induced apoptosis in cardiomyocytes
摘要
Abstract
Objective To explore the role of secreted phosphoprotein 1(SPP1)and myeloid differentiation primary response 88(MYD88)in morphine-induced cardiomyocyte apoptosis.Methods A morphine addiction model was established in Sprague-Dawley(SD)rats.Twelve SD rats were randomly assigned to the normal saline(NS)group or the morphine-dependent(DAM)group.Histopathological analysis was employed to observe and compare myocardial tissue morphology between the two groups.Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)staining was performed to assess the number of apoptotic cells in each group.The expression levels of SPP1 and MYD88 were evaluated using immunohistochemistry.Quantitative real-time poly merase chain reaction(RT-qPCR)and Western blot were used to detect the mRNA and protein expression of SPP1,MYD88,Bax,Bcl2,Caspase-3,and Caspase-9.Simultaneously,Western blot analysis was used to detected the expression of Cleaved Caspase-3 and Cleaved Caspase-9 proteins.In vitro,SPP1 expression was knocked down in primary neonatal rat cardiomyocytes(NRCMs),and cells were divided into three groups:control(CON),morphine treated(DA),and shSPP1#3+DA.Cell viability was assessed using the CCK-8 assay,and apoptosis rates were determined by flow cytometry.Results HE and TUNEL staining of myocardial tissues from morphine-addicted SD rats revealed that,compared with the NS group,myofibrils in the DAM group exhibited partial disruption and a significant increase in apoptotic cells(P<0.05).Western blot and RT-qPCR analyses demonstrated that,relative to the NS group,the mRNA and protein levels of SPP1,MYD88,Bax,Caspase-3,and Caspase-9 were significantly upregulated in the DAM group(P<0.05),whereas Bcl2 expression was significantly downregulated at both mRNA and protein levels(P<0.05),and the protein expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 were also increased.with all differences being statistically significant.In NRCMs following morphine intervention,cell viability in the DA group was markedly reduced compared to the CON group(P<0.05),accompanied by a signifi-cant increase in apoptosis rate(P<0.05).Consistently,Western blot and RT-qPCR results showed elevated mRNA and protein expression of SPP1,MYD88,Bax,Caspase-3,and Caspase-9 in the DA group(P<0.05),along with decreased Bcl2 expression(P<0.05).The protein expression levels of Cleaved Caspase-3 and Cleaved Caspase-9 were elevated simultaneously.In contrast,the shSPP1#3+DA group exhibited opposing trends compared to the DA group,with statistically sig nificant differences(P<0.05).Conclusion SPP1 and MYD88 play critical roles in mediating morphine-induced cardiomyocyte apoptosis,and silencing SPP1 has been shown to significantly reduce the extent of cardiomyocyte apoptosis following morphine exposure.关键词
心肌细胞/凋亡/二乙酰吗啡/分泌型磷蛋白1/髓样分化因子88Key words
cardiomyocytes/apoptosis/diacetylmorphine/SPP1/MYD88分类
医药卫生引用本文复制引用
刘静宇,陈少帅,蒲红伟,戴晨璐,季敏,苏丽萍,梁敏,程明,刘轩铭,张琳琳,郜玉洁..分泌型磷蛋白1、髓样分化因子88在二乙酰吗啡致心肌细胞凋亡中的作用[J].实用医学杂志,2025,41(22):3510-3519,10.基金项目
国家自然科学基金地区科学基金(编号:82160055) （编号:82160055）
新疆医科大学第一附属医院青年科研启航专项基金(编号:2023YFY-QKQN-37) （编号:2023YFY-QKQN-37）
新疆医科大学第一附属医院卓越人才计划项目 （）
新疆医科大学科研创新团队项目(编号:XYD2024C05) （编号:XYD2024C05）
