颅内动脉瘤患者血清差异表达蛋白质的研究

Sporadic intracranial aneurysms in patients with relatively proteomics research

目的 采用蛋白质组学方法研究散发性颅内动脉瘤和健康成人外周血清蛋白表达差异.方法 对散发性颅内动脉瘤和健康成人的血清样本进行双向凝胶电泳分离,通过对两种蛋白图谱的比较,确定差异表达的蛋白点 而后对差异点进行基质辅助激光解析电离飞行时间质谱分析和蛋白数据库信息检索 随机选取2种蛋白进行Western blot法验证蛋白质组学实验结果.结果 在颅内动脉瘤和健康成人中鉴定出14种差异表达蛋白,得到了11个肽质量指纹图谱（peptide mass fingerprinting,PMF）,最终7种蛋白质得到确认.结合珠蛋白、C反应蛋白、B因子、淀粉样血清蛋白A和载脂蛋白E前体在动脉瘤组表达上调 载脂蛋白A-Ⅳ前体和间α胰蛋白酶抑制物H4重链前体表达下调.蛋白印迹实验结果与双向电泳结果一致.结论 成功鉴定出7个与颅内动脉瘤相关的蛋白,为进一步阐明颅内动脉瘤形成的病理生理学机制提供了新的思路.

Objective To find out the differences on the protein expressions between human intracranial aneurysm and normal adult by way of proteomics. Methods The blood serums were obtained from sporadic aneurysms and normal adults,and then separated by two-dimensional gel electrophoresis（2-DE）. And the differential protein spots were identified by comparing the aneurysms and normals. And then to analyze the differential protein spots by matrix-assisted laser desorption ionization-time of flight-mass spectrometry（MALDI-TOF-MS） and The Protein Structure Database. The results were further validated by Western blot on the two selected proteins. Result Fourteen differential proteins were successfully identified, which were expressed significantly and differently in aneurysms and in controls, 11 peptide mass fingerprinting were received, and seven kinds of proteins were recognized. Haptoglobin, C-reactive protein, B factors, serum amyloid protein A and apolipoprotein E precursor group in the expression of aneurysms increased, while Apolipoprotein A-Ⅳ precursors and inter-α trypsin inhibitor heavy chain H4 precursor expression declined. The results of Western blotting were consistent with those of 2D-PAGE.Conclusion Seven proteins were identified with cerebral aneurysms, intracranial aneurysms in order to further clarify the pathophysiological mechanism of the formation of a new idea.