目的观察精神分裂症患者服用利培酮前后体内DISC1基因表达水平的变化,检测利培酮血药浓度,分析不同血药浓度对应的DISC1基因表达量,探讨利培酮的作用机制。方法选择闽南地区精神分裂症患者32例,抽取患者外周静脉血,离心后分离血浆和血细胞,采用高效液相色谱—质谱联用(HPLC-MS/MS)测量利培酮血药浓度,利用实时荧光定量PCR检测DISC1基因的表达。结果精神分裂症患者服用利培酮之后,体内DISC1基因表达水平升高(ΔCt=7.82),与服用利培酮之前的表达水平相比(ΔCt=11.85),差异具有统计学意义(t=11.08,P<0.05);利培酮血药浓度的标准浓度<130者17例,>130者12例,其对应的平均ΔCt值分别为8.61和6.72,两者差异具有统计学意义(t=3.91,P<0.05)。结论利培酮血药浓度与DISC1基因mRNA表达水平呈正相关,利培酮可能通过促进DISC1基因表达对精神分裂症患者起到治疗作用。
Objective To explore the change of DISC1gene expression in patients with schizophrenia pretherapy and post-treatment with risperidone,and detect the blood concentration of risperidone at the same time,to analyze the different blood concentration of risperidone corresponding to the DISC1gene expression level,in order to discuss the mechanism of risperidone.Methods32schizophrenia patients were selected from southern region of Fujian.Peripheral blood collected and divided into plasma and blood cell by centrifuge.The blood concentration of risperidone was detected by HPLC-MS/MS and DISC1mRNA level was evaluated by real time-PCR.Results The expression level of DISC1gene was increased after taking risperidone in patients with schizophrenia(ΔCt=7.82)compared with that prior treated with risperidone(ΔCt=11.85),the difference was significant(t=11.08,P<0.05).The normalized concentrations of risperidone lower than130was17cases,and higher than130was12cases,the corresponding average value ofΔCt was8.61and6.72respecticely,there was also significantly difference between them(t=3.91,P<0.05).Conclusion The blood concentration of risperidone and mRNA expression level of DISC1gene are positively correlated,risperidone may show treatment effect on patients with schizophrenia through promoting DISC1gene expression.