CAJ | 학술논문

目的采用药理学功能磁共振成像技术(phfMRI)研究鼻喷给药途径下中枢镇痛药物激活人脑的功能部位及作用机制.方法 18名右利手健康志愿者.试验药物为酒石酸布托啡诺鼻喷剂.行为学试验中记录受试者主观感受及药物作用时间,两周后行正式fMRI检查.采用组块设计,试验任务分两次EPI扫描(鼻喷药后7 min和25 min),共完成143次扫描.EPI扫描时给予试验者手背痛刺激.试验数据采用Matlab 6.5及SPM 2等软件行后处理获得脑功能图像.结果 ①该药起效作用时间集中在鼻喷药后15～35 min,与酒石酸布托啡诺药时曲线相近.②该药作用于人脑受体分布的相关激活脑区主要位于:皮层区:额叶(眶额回、额内上回、额上回)、颞叶(脑岛、颞中回、颞下回)、顶叶(楔前回)、边缘系统(扣带前回、扣带中回、海马、海马旁回)等;皮层下区(苍白球);小脑(小脑皮层6～9区、小脑脚、小脑蚓部).③多数受试者第二阶段激活脑区数量与程度强于第一阶段(P＜0.01).结论 phfMRI观察和研究经鼻腔给药后脑功能激活区及其机制是可行的.酒石酸布托啡诺鼻喷剂脑功能试验验证了人脑中枢神经系统阿片受体主要分布区及其可能的作用机制.
목적 채용약이학공능자공진성상기술(phfMRI)연구비분급약도경하중추진통약물격활인뇌적공능부위급작용궤제.방법 18명우리수건강지원자.시험약물위주석산포탁배낙비분제.행위학시험중기록수시자주관감수급약물작용시간,량주후행정식fMRI검사.채용조괴설계,시험임무분량차EPI소묘(비분약후7 min화25 min),공완성143차소묘.EPI소묘시급여시험자수배통자격.시험수거채용Matlab 6.5급SPM 2등연건행후처리획득뇌공능도상.결과 ①해약기효작용시간집중재비분약후15～35 min,여주석산포탁배낙약시곡선상근.②해약작용우인뇌수체분포적상관격활뇌구주요위우:피층구:액협(광액회、액내상회、액상회)、섭협(뇌도、섭중회、섭하회)、정협(설전회)、변연계통(구대전회、구대중회、해마、해마방회)등;피층하구(창백구);소뇌(소뇌피층6～9구、소뇌각、소뇌인부).③다수수시자제이계단격활뇌구수량여정도강우제일계단(P＜0.01).결론 phfMRI관찰화연구경비강급약후뇌공능격활구급기궤제시가행적.주석산포탁배낙비분제뇌공능시험험증료인뇌중추신경계통아편수체주요분포구급기가능적작용궤제.
Objective To investigate the regional cerebral stimulation after central analgesics nasal spray and its mechanism with pharmacological functional magnetic resonance imaging (phfMRI). Methods Eighteen healthy right-handed volunteers participated. Butorphanol tartrate nasal spray was used as the experiment agent. Ethological experiment was carried out to record the participants' subjective feeling and the onset time of the analgesics, followed by the functional MRI (fMRI) scan two weeks later. Block design was adopted. Two phases of fMRI scan were performed at 7 min and 25 min after the nasal spray, respectively. Participants were also given pain stimulation in the dorsum of hand during the fMRI scanning. The data were post-processed with Matlab 6.5 and SPM 2. Results ①Onset time of butorphanol tartrate was 15-35 min after nasal spray administration, which was consistent with its concentration-time curve. ②After nasal spray, activations were observed in the cerebral cortex, including frontal lobe (orbitofrontal gyrus, medial frontal gyrus, superior frontal gyrus), temporal lobe (insula, middle temporal gyrus, inferior temporal gyrus), parietal lobe (precuneal gyrus), limbic system (anterior cingulate gyrus, middle cingulate gyrus, hippocampus, parahippocampal gyrus);subcortical region (globus pallidus) and cerebellum (6-9 of cerebellar cortex, cerebellar peduncle, vermis). ③The number and activation intensity of the second phase were more obvious than those of the first phase (P<0.01). Conclusion The feasibility of phfMRI study on cerebral stimulation and the mechanism of nasal spray is demonstrated. The study of butorphanol tartrate further validates the main distribution of opioid receptors in the central nervous system and the possible mechanism of central analgesia.