二乙酰吗啡干预下大鼠心肌细胞蛋白质组学差异性研究  

Proteomic difference of rat cardiomyocytes under the intervention of diacetylmorphine

作　　者：王维娜[1] 刘丽 苏丽萍[3] 季敏 蒲红伟[4] WANG Weina;LIU Li;SU Liping;JI Min;PU Hongwei(Department of Pathology,Affiliated Tumor Hospital,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China;School of Basic Medicine,Xinjiang Medical University,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China;Department of Pathology,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China;Subject Construction Department,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China)

机构地区：[1]新疆医科大学附属肿瘤医院病理科,乌鲁木齐830011 [2]新疆医科大学基础医学院,乌鲁木齐830011 [3]新疆医科大学第一附属医院病理科,乌鲁木齐830011 [4]新疆医科大学第一附属医院学科建设科,乌鲁木齐830011

出　　处：《新疆医科大学学报》2021年第11期1209-1214,共6页Journal of Xinjiang Medical University

基　　金：国家自然科学基金(81860049)。

摘　　要：目的观察二乙酰吗啡干预下大鼠心肌细胞差异蛋白质组学的表达情况。方法SPF级SD大鼠乳鼠60只,提取心脏组织,体外培养原代心肌细胞,分正常对照组(Con)与药物干预组(Drug),Drug组使用10-4mol/L的二乙酰吗啡,Con组使用等量PBS作用24 h,提取2组心肌细胞中的总蛋白采用TMT定量蛋白质组学技术进行分析。结果蛋白质组学研究结果显示,大鼠心肌细胞中共鉴定出5884个蛋白质。2组总差异蛋白质784个,其中上调差异表达蛋白质442个,下调差异表达蛋白质342个。基因本体(GO)功能富集分析结果显示,差异表达蛋白质介导细胞生长过程、代谢过程、生物调节过程及对刺激的反应等重要生物学过程;基因百科全书(KEGG)通路富集分析显示,差异蛋白质集中于心肌收缩通路、钙信号通路、心肌细胞的肾上腺素能信号转导通路、致心律失常性右室心肌病及氧化磷酸化通路等。同时,差异蛋白质与心肌收缩密切相关,包括细胞膜二氢吡啶受体(DHPR)、肌浆网兰诺定受体2(RyR2)、三联蛋白Triadin(TRDN)、肌集钙蛋白2(CASQ2)以及肌钙蛋白I(TnI)等。结论二乙酰吗啡干预下大鼠心肌细胞差异蛋白质组学改变可能与心肌收缩节律异常、心肌细胞能量代谢及功能障碍等密切相关,以上差异蛋白的研究有望为临床上吸食二乙酰吗啡导致的心血管损伤提供新的理论参考和治疗靶点。Objective To observe the effect of diacetylmorphine on the expression of differential proteomics in rat car⁃diomyocytes.Methods A total of 60 SD rats were used to extract heart tissue and culture primary cardiomyocytes in vi⁃tro.They were divided into normal control group(Con)and drug intervention group(drug).The drug group was treated with 10-4mol/L diacetyl morphine,and the Con group was treated with the same amount of PBS for 24 hours.Total pro⁃teins were extracted from cardiomyocytes of the two groups and analyzed by TMT quantitative proteomics.Results The amount of 5884 proteins were identified in rats.A total of 784 differentially expressed proteins were found in the Con and drug groups,in which there were 442 up-regulated proteins and 342 down regulated proteins in the Con group and drug intervention group.GO functional enrichment found that the functions of these differentially expressed proteins are mainly to mediate important biological processes including cell growth processes,metabolic processes,biological regulatory processes,response to stimulation;KEGG pathway enrichment analysis showed that these proteins mainly focus on the myocardial contractile pathway,calcium signaling pathway,adrenergic signaling transduction pathway in cardiomyocytes,arrhythmiogenic right ventricular cardiomyopathy and oxidative phosphorylation pathways.Several dif⁃ferential proteins are closely associated with myocardial contraction,including DHPR,RyR2,TRDN,CASQ2,TnI,and etc.Conclusion The differential proteomic changes of rat cardiomyocytes under the intervention of diacetylmorphine may be closely related to the abnormal cardiac contractile rhythm and dysfunction of cardiomyocytes.The study of the above differential proteins may provide a new theoretical reference and therapeutic target for cardiovascular injury in⁃duced by diacetylmorphine in clinical.

关 键 词：二乙酰吗啡 心肌细胞 蛋白质组学 

分 类 号：R453[医药卫生—治疗学]