首发精神分裂症患者利培酮治疗前后外周血浆蛋白质组学观察

Proteomic analysis of novel serum markers in first-episode schizophrenics before versus aftertreatment of risperidone

目的观察精神分裂症患者利培酮治疗前后外周血浆中蛋白质表达的变化，寻求潜在疾病诊断、治疗及药物不良反应相关的标志物。方法收集来自2011年1—12月于郑州大学第一附属医院就诊的80例首发精神分裂症患者，单一利培酮治疗8周。于治疗前及治疗8周末检测血脂、血糖，抽取晨空腹外周血分离血浆，选取15例患者血浆经过二维凝胶电泳（2-DE）、MALDI-TOF质谱分析并与蛋白质数据库对比确定差异表达的蛋白质，并应用ELISA检测所有样本差异表达蛋白质的变化。结果15例患者治疗前后蛋白质的表达量相差1．2倍以上共计23个。质谱分析后得出治疗后载脂蛋白A1（APOA-1）等9个蛋白质表达上调，触珠蛋白（HP）等8个蛋白质表达下调。所有患者ELISA结果显示，APOA-1及HP水平治疗前[APOA．1：（4．72±0．03）ng／ml；HP：（56．66±0．13）ng／ml]与治疗后[APOA-1：（5．14±0．06）ng,／ml；HP：（55．18±0．17）ng／ml]相比差异有统计学意义（P〈0．01）。结论治疗后外周血中血脂代谢及免疫相关的蛋白质发生改变，为临床医生根据这些血浆蛋白的变化监测抗精神病药物的不良反应提供了理论依据。

Objective To explore the changes in serum protein levels of schizophrenics before and after treatment of risperidone and identify the potential markers of diagnosis, treatment and drug side effects of schizophrenia. Methods Eighty first-episode schizophrenics without other concurrent diseases and with positive and negative symptom scale （PANSS） score greater than or equal to 60 were recruited. And 15 of them were measured by proteomics. Different serum levels of proteins were obtained from these patients and were separated by two-dimensional electrophoresis （2-DE） before and after a single risperidone treatment for 8 weeks. These proteins were then identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF-MS） and peptide mass fingerprinting. Enzyme-linked immunosorbent assay （ELISA） was used to verify the resuhs. Results Almost 1400 spots were detected by 2-DE in each gel. Of these proteins, 23 protein spots showed significant differences in abundance before and after risperidone treatment. After MALDI-TOF peptide mass fingerprinting, 9 up-regulated proteins and 8 down-regulated proteins were validated after treatment. Of these proteins, the schizophrenics showed a significantly higher content of apolipoprotein A-1 （ APOA-1 ） than those before treatment and haptoglobin （HP） protein was down-regulated after treatment. The results of ELISA were parallel with those of proteomic （ P 〈 0.01 ）. Conclusion The serum proteins correlated with blood glucose and lipid metabolism are altered in schizophrenia after treatment of risperidone. A clinician should monitor the side effects of antipsychotic drugs according to the changes of serum proteins.