高血压脑出血患者脑脊液差异蛋白组学研究

Differential proteomic analysis of cerebrospinal fluid proteins in patients with hypertensive intracerebralhemorrhage

目的筛选出与高血压脑出血密切相关的疾病特异性蛋白，探讨其在高血压脑出血发病机制中的作用。方法应用表面增强激光解吸离子化飞行时间质谱（SELDI-TOF-MS）技术检测69例脑脊液标本的蛋白质谱，其中健康对照者15例、高血压患者10例、高血压脑出血术前患者24例、高血压脑出血术后患者20例。比较分析高血压脑出血术前组与高血压组、高血压脑出血术前组与术后组、健康对照组与高血压组脑脊液蛋白质谱。用BiomarkWizard软件分析其差异蛋白质峰，并通过蛋白数据库检索出与高血压脑出血密切相关的疾病特异性蛋白。结果通过比较分析高血压脑出血术前组与高血压组、高血压脑出血术前组与术后组、健康对照组与高血压组脑脊液蛋白质谱，分别筛选出23个、16个、0个差异蛋白质峰。高血压脑出血术前组与高血压组问的23个差异蛋白质峰中有6个差异峰有重要意义，与这6个差异峰相对分子质量接近的蛋白质分别为B型脑钠肽、中性粒细胞防御素2、活性氧自由基、亚型戊烯半胱氨酸氧化酶、分泌载体相关的膜蛋白SCAMP4、白介素-31。结论通过分析高血压脑出血患者脑脊液蛋白质谱，可以筛选出与高血压脑出血相关的疾病特异性蛋白，其能成为预测高血压脑出血的分子标志物。

Objective To compare the proteomic spectrum of cerebrospinal fluid between patients with hypertensive cerebral hemorrhage before surgery and patients with hypertension, between patients with hypertensive cerebral hemorrhage before surgery and atter surgery, between healthy controls and patients with hypertension, and find out disease-specific proteins （DSPs） closely correlated with hypertensive cerebral hemorrhage to explore their roles in hypertensive cerebral hemorrhage. Methods Sixty-nine cerebrospinal fluid samples fi＇om patients with hypertensive cerebral hemorrhage （before operation, n=24; after operation, n=20）, from patients with hypertension （n=10）, and from healthy controls （n=15） were detected by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry （SELDI-TOF-MS）. Data were analyzed by Biomark Wizard software（Ciphergen Inc.）, and DSPs closely correlated with hypertensive cerebral hemorrhage were searched by protein databases. Results By comparing and analyzing the proteomic spectrum of patients from group of hypertensive cerebral hemorrhage before surgery and group of hypertension, from groups of hypertensive cerebral hemorrhage before surgery and after surgery, from group of healthy controls and group of hypertension,the candidate protein peaks were screened, and the number of them was 23, 16, and 0, respectively. The 23 different protein peaks between patients with hypertensive cerebral hemorrhage before surgery and patients with hypertension were analyzed by Biomarker pattern software, showing 6 different protein peaks were important; through searching the database according to molecular weight, we noted that these protein might be brain natriuretic peptide （BNP）, human neutrophil peptide alpha-defensin （HNP-2）, reactive oxygen species （ROS）, PCYOX, secretory carrier membrane protein 4 （SCAMP4） and interleukin-31. Conclusion Differentially expressed proteins from patients with hypertensive cerebral hemorrhage could be screened after analyzing the map of cerebrospinal fluid protein mass spectrum, and these differentially expressed proteins are expected to be the molecular markers to forecast hypertensive cerebral hemorrhage.