MRI离子示踪动态监测多脏器损伤细胞内Ca2+的变化

Intracellular calcium overload is thought to be the key link of secondary whole-body multiple organ injury caused by variety of factors (e.g. shock, severe multiple trauma and infection, etc) and final common pathway of cell death induced by many kinds of agents. Early in vivo detection of calcium overload is the precondition of preventing the whole-body multiple organ injury due to the various causes. However, there is no an effective approach to in vivo detect intracellular calcium overload at present. In this subject, through use rat model of hemorrhagic shock for example, mainly focus on exploring the Mn2+ simulating Ca2+ MRI ion tracer technique and applying it to dynamic monitor the intracellular Ca2+ change of the rat whole-body vital organs underwent hemorrhagic shock, and compare with the histopathologic, immunofluorescence Ca2+ imaging and routine MRI (include T2*-Map, DWI and DTI) findings, to explore the intracellular Ca2+ change rule of the whole-body vital organs, and identify the concordance between the Mn2+ simulating Ca2+ MRI ion tracer results and the immunofluorescence Ca2+ imaging, histopathologic and routine MRI findings. Finally, we hope to found a new imaging technique for early, noninvasive, dynamic, in vivo monitoring the various causes-induced whole-body multiple organ injury and intracellular Ca2+ change and establish standard detecting method and mathematical model.

细胞内Ca2+超载是各种原因(如休克、多发伤、严重感染等)导致全身多脏器损伤的关键环节，也是多种原因引起细胞损害的最后共同通路。对细胞内Ca2+超载进行早期活体检测是防治各种原因继发全身多脏器损伤的前提，但目前尚未找到合适的体内检测细胞内Ca2+超载的有效方法。本项目拟以失血性休克大鼠模型为例，重点研究Mn2+模拟Ca2+ MRI离子示踪技术及其对全身重要脏器细胞内Ca2+变化的动态监测，并与组织病理学、免疫荧光Ca2+检测结果及常规MRI(T2*-Map, DWI及DTI)表现进行对照，以探索重要脏器损伤细胞内Ca2+的变化规律，并验证Mn2+模拟Ca2+ MRI离子示踪技术与组织病理学、免疫荧光Ca2+检测结果及常规MRI表现之间的一致性，希望为开创一种早期、无创、活体动态监测各种原因导致全身多脏器损伤细胞内Ca2+变化的影像学新技术奠定基础，并建立标准的检测方法和数学模型。

细胞内Ca2+超载是各种原因(如休克、多发伤、严重感染等)导致全身多脏器损伤的关键环节，也是多种原因引起细胞损害的最后共同通路。对细胞内Ca2+超载进行早期活体检测是防治各种原因继发全身多脏器损伤的前提，但目前尚未找到合适的体内检测细胞内Ca2+超载的有效方法。本项目以失血性休克大鼠模型为例，重点研究了Mn2+模拟Ca2+ MRI离子示踪技术及其对全身重要脏器细胞内Ca2+变化的动态监测。通过系列研究建立了Mn2+模拟Ca2+ MRI离子示踪技术活体动态监测全身多脏器损伤细胞内Ca2+变化的标准检查程序和方法；验证了Mn2+模拟Ca2+ MRI离子示踪技术动态监测失血性休克肝细胞内Ca2+变化的准确性；发现了细胞内Ca2+超载程度与大鼠失血性休克脏器损伤严重度之间的关系，及其与细胞内Mn2+含量质谱分析结果之间的一致性。该项目已在国内外专业学术期刊发表相关论文6篇，研究结果多次在国内外学术会议进行大会发言。我们的研究达到预期目标，为开创一种早期、无创、活体动态监测各种原因导致全身多脏器损伤细胞内Ca2+变化的影像学新技术奠定了基础，并建立了标准的检测方法。