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目的 对Tau蛋白病患者与4例正常老年人尸检脑标本进行蛋白质组学研究以期了解Tau蛋白病分子机制并寻找诊断治疗该疾病的蛋白质标记物。方法 颞叶蛋白质以固相pH梯度等电聚焦为第一向,SDS PAGE垂直电泳为第二向进行双向电泳(2 DE),分析电泳图谱,基质辅助激光解析/电离飞行时间(MALDI TOF)质谱或MALDI TOF/TOF串联质谱鉴定蛋白质。结果 18种蛋白质的表达量在Tau蛋白病患者与正常老年人显著不同。分别被鉴定为3 磷酸甘油醛脱氢酶、尿嘧啶DNA糖苷水解酶、Cu Zn超氧化物歧化酶、异柠檬酸脱氢酶亚单位、synaptotagminI、Peroxiredoxin2、胶质纤维酸性蛋白、p25α、烯酰辅酶A水合酶短链1、吡哆醇5′磷酸氧化酶、Mn超氧化物歧化酶、α烯醇化酶、抗氧化蛋白2、铁蛋白H链、谷氨酸脱氢酶、肽基脯氨酸顺反异构酶A、血清白蛋白前体、二氢嘧啶酶相关蛋白2。结论 上述差异蛋白有助于深入理解Tau蛋白病机制并有望在Tau蛋白病的早期诊断及新药开发上发挥作用。
OBJECTIVE: To study the proteomics of Tau proteinuria patients and four normal elderly autopsy brain samples in order to understand the molecular mechanism of Tau proteinuria and to search for protein markers for diagnosis and treatment of the disease. METHODS: The temporal lobe proteins were characterized by isoelectric focusing on solid-phase pH gradient as the first direction and SDS PAGE as the second direction by two dimensional electrophoresis (2 DE). Electrophoresis, MALDI-TOF mass spectrometry Or MALDI TOF / TOF tandem mass spectrometry. Results The expression levels of 18 kinds of proteins were significantly different between patients with Tauopathy and normal controls. Were identified as glyceraldehyde 3 phosphate dehydrogenase, uracil DNA glycoside hydrolase, Cu Zn superoxide dismutase, isocitrate dehydrogenase subunit, synaptotagmin I, Peroxiredoxin 2, glial fibrillary acidic protein, p25 alpha, CoA Hydratase Short Chain 1, Pyridoxine 5 ’Phosphate Oxidase, Mn Superoxide Dismutase, Alpha Enolase, Antioxidant 2, Ferritin H Chain, Glutamate Dehydrogenase, Peptide Proline Acid cis-trans-isomerase A, serum albumin precursor, dihydropyrimidinase-related protein 2. Conclusion The above differential proteins help to understand the mechanism of Tau protein pathogenesis and are expected to play an important role in the early diagnosis of Tau protein and the development of new drugs.