MEMRI监测早期多器官功能障碍综合征细胞内Ca2+变化的研究进展

摘要

锰离子(manganese,Mn2+)作为一种磁共振成像(magnetic resonance imaging,MRI)对比剂在动物实验中的应用已有30余年,由于其对多种生物学过程敏感,近年来Mn2+增强MRI(Mn2+-enhanced MRI,MEMRI)在生物学研究中取得了一些进展,主要包括细微解剖结构的对比增强、功能区活动诱导Mn2+依赖MRI(activity-induced manganese-enhanced MRI,AIM-MRI)和神经环路或特殊神经元连接的束路示踪3个方面.MEMRI的应用主要基于Mn2+3个特性:Mn2+作为钙离子(calcium,Ca2+)的类似物可经L型电压门控钙通道进入可兴奋细胞内;其顺磁性可造成水质子T1弛豫时间缩短,引起T1WI信号的正比增强;Mn2+进入神经细胞内可基于微管依赖的轴向转运进行跨突触传递至邻近神经元.多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS)的死亡率极高,了解其发生机制并及时阻断其发展进程是治疗MODS的切入点.细胞内Ca2+超载是引起MODS发生的关键事件之一,基于Mn2+的生物学特性,MEMRI有潜力活体动态监测早期MODS发生过程相关病理生理学改变,为进一步探索其发生机制和评估疗效提供可能.%Manganese ion (Mn2+) has been applied for quite a few animal experiments for more than thirty years as a contrast agent of magnetic resonance imaging (MRI), duo to its sensitivity for a number of biological processes, manganese-enhanced MRI (MEMRI) made great progress in a multitude of biological researches in recent years, mainly including three aspects: contrast enhancement of subtle anatomical structure, activity-induced manganese-enhanced MRI (AIM-MRI) and tracing neural circuits or special neuronal connectivity. The application of MEMRI is primarily based on the following three properties of Mn2+: as an analogue of calcium ion (Ca2+), Mn2+ could enter into excitable cells via L-type voltage gated calcium channels; paramagnetic Mn2+ can shorten longitudinal relaxation time of water protons and result in positive MRI T1 enhancement effect; Mn2+ entered into neurons and can traverse synapses to accumulate in neighboring neurons by microtubule-dependent axonal transport. Multiple organ dysfunction syndrome (MODS), has a very high mortality rate, and it is a pointcut for the treatment of MODS to understand its mechanisms and timely to hinder the developing process. Intracellular Ca2+ overload is one of the key events during MODS, and basing on the relative biological properties of Mn2+, MEMRI might have the potential to monitor dynamically some relative pathophysiological progresses at the early stage of MODS in vivo, and it's possible to further explore its mechanisms and evaluate effect of treatment.