CAJ | 학술논문

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.手治疗前及治疗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.
목적 관찰정신분렬증환자리배동치료전후외주혈장중단백질표체적변화,심구잠재질병진단、치료급약물불량반응상관적표지물.방법 수집래자2011년1-12월우정주대학제일부속의원취진적80례수발정신분렬증환자,단일리배동치료8주.수치료전급치료8주말검측혈지、혈당,추취신공복외주혈분리혈장,선취15례환자혈장경과이유응효전영(2-DE)、MALDI-TOF질보분석병여단백질수거고대비학정차이표체적단백질,병응용ELISA검측소유양본차이표체단백질적변화.결과 15례환자치료전후단백질적표체량상차1.2배이상공계23개.질보분석후득출치료후재지단백A1(APOA-1)등9개단백질표체상조,촉주단백(HP)등8개단백질표체하조.소유환자ELISA결과현시,APOA-1급HP수평치료전[APOA-1:(4.72±0.03)ng/ml;HP:(56.66±0.13)ng/ml]여치료후[APOA-1:(5.14±0.06)ng/ml;HP:(55.18 ±0.17)ng/ml]상비차이유통계학의의(P＜0.01).결론 치료후외주혈중혈지대사급면역상관적단백질발생개변,위림상의생근거저사혈장단백적변화감측항정신병약물적불량반응제공료이론의거.
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 results.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.