多发性硬化患者脑脊液蛋白质组学研究

Proteomics Analysis of Cerebrospinal Fluid among Multiple Sclerosis Patients

目的探讨多发性硬化(MS)发病的分子机制并寻找其脑脊液(CSF)蛋白质标志物。方法对MS患者与紧张型头痛患者各6例的CSF蛋白质组学进行比较研究。将浓缩的CSF去除高丰度蛋白后行双向凝胶电泳,对凝胶图谱进行图像分析,探寻差异性蛋白点并经肽质量指纹质谱技术鉴定蛋白质点。结果 MS患者38种蛋白质的表达与对照组比较差异有统计学意义(P<0.05),部分差异性蛋白质经鉴定为白蛋白单体CRA_n、ATP合成酶、普通转录因子ⅡH、白蛋白单体CRA_j、四连接素、结合珠蛋白、丛生蛋白、富亮氨酸α-2糖蛋白、视黄醇结合蛋白与甲状腺素结合蛋白。结论 MS患者CSF多种蛋白质表达差异,可能存在能量代谢异常、炎症反应和组织修复机制。

Objective To investigate the molecular mechanism and marker proteins of multiple sclerosis in human cerebrospinal fluid（CSF）. Methods A comparative proteomic analysis of CSF protein was employed to 6 patients with multiple sclerosis（MS） and compared with 6 controls. After the depletion of high-abundance protein from CSF, two-dimensional gel electrophoresis and peptide mass fingerprinting（PMF） were used to identify the differential proteins. Results The gels containing MS CSF revealed 38 spots that were different from the control gels. Ten of the differential spots were chosen to be identified with PMF. Seven of those were proteins present in normal human CSF. They were haptoglobin, clusterin, leucine-rich alpha-2-glycoprotein, retinol binding protein, thansthyretin and albumin（isoform CRA_n and isoform CRA_j）. The three exceptions were ATP synthase, general transcription factor ⅡH and tetranectin. Conclusions It suggested that the mechanism of MS should be closely related to the damage of energy metabolic pathway, inflammation, reconstruction of tissue.