Molecular pathology of brain matrix metalloproteases, claudin5, and aquaporins in forensic autopsy cases with special regard to methamphetamine intoxication
Molecular pathology of brain matrix metalloproteases, claudin5, and aquaporins in forensic autopsy cases with special regard to methamphetamine intoxication
复制标题
DOI：
10.1007/s00414-014-0972-6
复制
发表时间：
2014-02
影响因子：
2.1
通讯作者：
Qi Wang;T. Ishikawa;T. Michiue;B. Zhu;D. Guan;H. Maeda
中科院分区：
文献类型：
--
作者：
Qi Wang;T. Ishikawa;T. Michiue;B. Zhu;D. Guan;H. Maeda
甲基苯丙胺是一种高度成瘾的滥用毒品，对大脑有毒性。最近的研究表明，除了对多巴胺和5-羟色胺终末的直接损伤外，冰毒的神经毒性也可能是由于其改变血脑屏障(BBB)的结构所致。本文研究了一氧化碳(n= )14例、冰毒(n= 21)和苯巴比妥(n= 17)法医尸检病例与机械性窒息(n= 15)、脑损伤( 11)、非脑损伤(n= 21)和锐器损伤(n= 15)的脑组织中基质金属蛋白酶(MMPs)、CLDN5和水通道蛋白(AQPs)的表达。Taqman实时荧光定量分析显示AQP4和MMP9在冰毒患者中高表达，CLDN5低表达，而MMP2在苯巴比妥中毒患者中低表达。免疫染色结果显示，每组患者的个体间差异很大，在所有死因的分布或强度上没有明显差异。这些结果表明，冰毒可能通过改变CLDN5和MMP9而增加血脑屏障通透性，并可能通过上调AQP4来激活自我保护系统以消除脑细胞外间隙的积水。利用实时定量聚合酶链式反应对基因表达进行系统分析在法医死亡调查中可能是一种有用的程序。
Methamphetamine (METH) is a highly addictive drug of abuse and toxic to the brain. Recent studies indicated that besides direct damage to dopamine and 5-HT terminals, neurotoxicity of METH may also result from its ability to modify the structure of blood-brain barrier (BBB). The present study investigated the postmortem brain mRNA and immunohistochemical expressions of matrix metalloproteases (MMPs), claudin5 (CLDN5), and aquaporins (AQPs) in forensic autopsy cases of carbon monoxide (n= 14), METH (n= 21), and phenobarbital (n= 17) intoxication, compared with mechanical asphyxia (n= 15), brain injury (n= 11), non-brain injury (n= 21), and sharp instrument injury (n= 15) cases. Relative mRNA quantification using Taqman real-time PCR assay demonstrated higher expression of AQP4 and MMP9, lower expression of CLDN5 in METH intoxication cases and lower expression of MMP2 in phenobarbital intoxication cases. Immunostaining results showed substantial interindividual variations in each group, showing no evident differences in distribution or intensity among all the causes of death. These findings suggest that METH may increase BBB permeability by altering CLDN5 and MMP9, and the self-protective system maybe activated to eliminate accumulating water from the extracellular space of the brain by up-regulating AQP4. Systematic analysis of gene expressions using real-time PCR may be a useful procedure in forensic death investigation.