癫痫小鼠中髓过氧化物酶的SPECT-CT成像  

SPECT/CT imaging of myeloperoxidase in epileptic mice

作　　者：张祎年[1] 董华腾[3] 王泽青[1] 周俊林[2] 刘建莉[2] 张新定[1] 潘亚文[1] 

机构地区：[1]兰州大学第二医院神经外科,730030 [2]兰州大学第二医院放射科,730030 [3]甘肃省妇幼保健院小儿神经内科

出　　处：《中华神经外科杂志》2016年第10期1048-1053,共6页Chinese Journal of Neurosurgery

基　　金：国家自然科学基金（81501116）;甘肃省科技计划资助项目（1506RJZA228）;兰州市科技计划项目（2014-1-30）

摘　　要：目的 探讨髓过氧化物酶（MPO）在癫痫发生中的作用,并通过分子影像学手段对MPO进行活体成像以定位致痫灶,旨在为手术切除隐源性致痫灶提供依据.方法 通过腹腔注射匹罗卡品建立小鼠癫痫模型,应用MPO特异性抑制剂4-氨基苯甲酰肼（ABAH）进行干预,设立假诱导组、生理盐水治疗组和ABAH治疗组.采用MPO活性测定方法检测各组大脑内MPO的活性,以Western blot方法检测MPO的特异性蛋白产物,并通过伊文思蓝染色观察急性期癫痫小鼠血脑屏障的开放情况.应用SPECT-CT成像系统动态追踪小鼠脑内MPO的活性变化,采用放射自显影术离体对小鼠脑内MPO的活性进行定量检测,通过Timm染色进一步明确海马内苔藓纤维出芽的情况.结果 与假诱导组相比,癫痫小鼠大脑内MPO活性明显升高（P＞0.05）.与生理盐水治疗组相比,ABAH治疗组小鼠脑内MPO的活性及MPO特异性的蛋白产物含量均降低（P =0.016,P=0.016）.伊文思蓝染色结果显示,急性期癫痫小鼠血脑屏障的破坏在癫痫发生后24h达高峰.SPECT-CT成像显示,与假诱导组相比,生理盐水治疗组小鼠脑内MPO活性明显升高（P=0.010）;与生理盐水治疗组相比,ABAH治疗组小鼠脑内MPO活性降低（P=0.030）.离体放射自显影术检测结果表明,ABAH治疗组的MPO活性低于生理盐水治疗组（P＜0.05）.与生理盐水治疗组相比,ABAH治疗组海马苔藓纤维出芽明显减少（P=0.003）.结论 通过SPECT-CT结合特异性的分子探针可活体追踪癫痫小鼠脑内MPO活性改变.脑内MPO可能成为癫痫成像和靶向治疗的分子标志物.Objectives To investigate the role of myeloperoxidase （MPO） in epileptogenesis and to perform in vivo imaging of MPO noninvasively for localizing the epileptic foci by means of molecular imaging in order to provide the basis for surgical resection of cryptogenic epileptic foci.Methods A mouse epilepsy model was induced by intraperitoneal injection of pilocarpine.MPO specific inhibitor 4-aminobenzoic acid hydrazide （ABAH） was used to conduct the intervention.The false-induction group,saline treatment group and ABAH treatment group were set up.MPO activity assay was used to detect the MPO activity in the brain of each group.Western blot was used to detect the specific protein products of MPO,and Evans blue staining was used to observe the opening of blood-brain barrier in mice with acute epilepsy.Single photon emission computed tomography （SPECT） system was used to dynamically track the activity changes of MPO in the brains of mice.In vivo autoradiography was used to quantitatively detect the MPO activity in the brains of mice.The hippocampal mossy fiber sprouting was further clarified by Timm staining.Results Compared with the false-induction group,the activity of MPO in the brains of epileptic mice was increased significantly （P 〉 0.05）.Compared with the saline treatment group,the activity of MPO and the protein products of MPO specific protein in the brains of the mice of the ABAH treatment group were decreased （P =0.016,P =0.016）.The results of Evans blue staining showed that the damage of epileptic mouse blood-brain barrier in acute phase reached the peak at 24 h after the onset of epilepsy.SPECT-CT imaging showed that the MPO activity of the saline treatment group in the brains of mice increased significantly compared with the false-induction group （P =0.010）;the MPO activity in the brains of mice of the ABAH treatment group was decreased compared with the saline treatment group （P =0.030）.In vitro autoradiographic detection results showed that the activity of MPO in the ABAH tre

关 键 词：癫痫 髓过氧化物酶 体层摄影术 发射型计算机 单光子 体层摄影术 X线计算机 小鼠 

分 类 号：R742.1[医药卫生—神经病学与精神病学]