多维色谱串联质谱结合双向电泳分析阿替洛尔(r) - 第三军医大学学报.docVIP

双向电泳结合MDLC-MS/MS法分析阿替洛尔对映异构体作用后的血管平滑肌细胞差异表达蛋白 邱峰1郑姣妮邱宗荫Zorbax 300SB-C18富集柱和一支纳升级Zorbax 300SB-C18分析柱）富集、分离差异表达蛋白酶解后的肽混合物，线性离子阱质谱进行在线分析，Spectrum Mill MS Proteomics Workbench自动分析MS和MS/MS数据，通过UniProt KB / SWISS-PORT数据库进行搜索。结果 经与(R)-ATN干预VSMCs后的蛋白质组进行比较、筛选，(S)-ATN干预VSMCs后的蛋白质组中有6个蛋白质点表达上调。结论 所获得的6种差异表达蛋白中，除未定性蛋白C3orf19以外，其余5种蛋白质可能与心血管功能有关：CrK相关底物蛋白、接头蛋白-3复合物(-1亚基与细胞的信号传导与跨膜转运有关；线粒体苹果酸脱氢酶前体1、磷酸甘油醛脱氢酶与细胞能量代谢有关；内皮细胞清道夫受体2是介导乙酰化低密度脂蛋白修饰与降解过程的重要因子。 [关键词] 阿替洛尔；对映异构体；血管平滑肌细胞；蛋白质组；多维色谱；串联质谱Qiu Feng 1, Chen Shizhi 2, Zhen Jiaoni 3, Qiu Zongyin 3(1 Department of Pharmacy, First Affiliated Hospital of Chongqing Medical University, 2 Department of Medical Laboratory, Second Affiliated Hospital of Chongqing Medical University， 3College of Pharmacy, Chongqing Medical University, Chongqing 400016, China) [Abstract] Objective Chiral medicines selectively interact with biological macromolecules through strict chiral recognition and demonstrate different pharmacokinetic characteristics and drug effects. Methods In this study, differential protein expression was assessed in vascular smooth muscle cells (VSMCs) treated with R/S-enantiomers of atenolol. The differential expression protein spots from (R)/(S)-ATN treated VSMCs were screened by 2-DE, and were analyzed by on-line two-dimensional nano liquid chromatography (HPLC-CHIP included an enrichment column of Zorbax 300SB-C18 and an analytical column of Zorbax 300SB C18) coupled with linear ion trap mass spectrometry. Results There were six diferential proteins between VSMCs treated treated by (R)/(S)-ATN. Conclusion Six different expression proteins including enhancer of filamentation 1, AP-3 complex subunit beta-1, malate dehydrogenase, mitochondrial precursor, glyceraldehyde-3-phosphate dehydrogenase, uncharacterized protein C3orf19 were screened, and five proteins might be related to cardiovascular events. The results of the present study help to provide insight into the chiral drugs. [Key words] Atenolol; Enantiomers; Vascular