哌醋甲酯治疗注意缺陷多动障碍前后DRD4和DAT1基因mRNA表达的研究  

DRD4/DAT1 mRNA expression in attention deficit hyperactivity disorder children before and after methylphenidate treatment

作　　者：丁凯景[1] 康传媛[1] 刘瑞湘[1] 张艳[1] 刘华[1] 

机构地区：[1]昆明医科大学第一附属医院,昆明650032

出　　处：《中华行为医学与脑科学杂志》2015年第10期896-899,共4页Chinese Journal of Behavioral Medicine and Brain Science

基　　金：国家自然科学基金项目（30900488,81460218）;云南省高层次卫生技术人才培养专项经费项目（D-201238）;2012云南省卫生科技计划项目（2012ws0008）

摘　　要：目的探讨注意缺陷多动障碍（attentiondeficithyperactivitydisorder，ADHD）患儿服用哌醋甲酯前后外周血中多巴胺转运体基因（dopaminetransportergene／solutecarrierfamily6，member3，DATl／SLC6A3）和多巴胺D4受体基因（dopaminereceptorD4，DRD4）的mRNA表达水平的变化，探索其与症状严重程度、药物疗效的关系。方法共纳入符合美国《精神疾病诊断和统计手册》第4版（DSM-IV）ADHD诊断标准的6—15岁首诊的ADHD患儿45例，进行6周哌醋甲酯药物系统滴定，采用ADHD症状分级父母评定量表（ADHDratingscale—IVHomeVersion，ADHD—RS—IVhomeversion）、威斯康辛卡片分类测试（Wisconsincardsortingtest，WCST）、视觉注意力持续操作测验（visualcontinuousperformancetask，VCPT）进行临床症状和认知功能评定。采用试剂盒提取样本血总RNA并进行逆转录，采用实时荧光定量聚合酶链反应（quanti—tativerealtimepolymerasechainreaction，qRT—PCR）法测定两目的基因服药前后的mRNA相对表达量。结果ADHD患儿DRD4服药后的mRNA相对表达量（0．23±0．23）高于服药前（0．16±0．18）（P=0．041），而DAT1服药前的mRNA相对表达量（0．43±0．40）与服药后（0．39±0．53）差异无统计学意义（P〉0．05）；治疗有效组和无效组间两目的基因服药前相对表达量差异无统计学意义（均P〉0．05），服药前后mRNA表达变化倍数均差异无统计学意义（均P〉0．05）；基线DRD4基因mRNA相对表达量与CPT错判T分呈正相关（r=0．424，P=0．025），而与ADHD—RS—IV总分、WCST概念化水平、CPT漏判T分及反应时间T分均无统计学线性相关关系；基线DAT1mRNA相对表达量与ADHD—RS—IV总分、WCST慨念化水平和CPT成绩均无显著相关性（均P〉0．05）。结论本研究初步提示服用哌醋甲酯后ADHD患儿DRD4基因功能可能有提高。同时，该基因表达水平可能与ADHD患儿冲动症状有关，因此，DRObjective To investigate mRNA expression level changes of dopamine transporter gene （ DAT1 ） and dopamine receptor gene （DRD4） in attention deficit hyperactivity disorder （ ADHD ） children＇ s peripheral blood before and after methylphenidate treatment, and to explore associations between the mRNA expression level and symptom severity, as well as methylphenidate response. Methods Forty five ADHD children by DSM-IV diagnostic criteria,aged six to fifteen years old participated in a six-week drug titration treatment of methylphenidate. ADHD-RS-IV Home Version,WCST and VCPT were used to evaluate the ADHD clinical symptoms and cognitive functions. RNA Simple Total RNA Kit was used to extract the total RNA. After reverse transcription, the obtained c-DNA was used in the following qRT-PCR to evaluate relative mRNA expression of the candidate genges before and after medication. Results The DRD4 mRNA relative expression level after taking methylpheni- date was significantly higher than that before methylphenidate treatment （ 0.23 ±0.23 vs 0.16 ± 0.18, P = 0.041 ）. There was no significant difference between DAT1 mRNA relative expression level before （0.43± 0.40 ） and after （0.43-＋0.40） methylphenidate treatment. No significant difference was found on either basal DAT1/DRD4 mRNA expression or fold change of DAT1/DRD4 mRNA expression before and after medication between methylphenidate treatment responders and non-responders groups. There was a positively significant correlation between baseline DRD4 mRNA relative expression level and erroneous T score of CPT（ r= 0.424, P= 0.025） ,however, no other statistically significant correlation was found between basal DRD4 mRNA relative expression level and ADHD-RS-IVtotal score, WCST conceptual level, CPT missing T score, and CPT reaction T score（ all P〉0.05 ）. There was also no statistical significant correlation between basal DAT1 mRNA relative expression level and ADI-ID-RS-Ⅳ total score, WCST conceptual level,and CPT T scores（all P〉

关 键 词：注意缺陷多动障碍 哌醋甲酯 多巴胺D4受体基因 多巴胺转运体基因 MRNA表达 

分 类 号：R749.94[医药卫生—神经病学与精神病学]