非梗死区心肌纤维化的磁共振功能成像检测与TGF-β1表达水平的相关性研究

Left ventricular remodeling is an important pathological change after myocardial infarction. The most obvious changes of infarction zone are myocardial cell necrosis and scarring. Non-infarction myocardium also has series of alterations, including myocardial cell hypertrophy and apoptosis, myocardial fibers disorder, revascularization, interstitial collagen hyperplasia and so on. Cardiac dysfunction, as a result of these pathological changes, further deterioration to heart failure and death. The changes in non-infarction myocardium have become a new research hot spot, and the treatment of myocardial infarction has focused on protecting and repairing non-infarction myocardium structure and function. Therefore, assessing morphological and functional changes of non-infarction myocardium in reconstruction process has vital significance in the clinical, such as draw up treatment strategies and evaluation of curative effect. This study has employed high field strength MRI imaging with animal special coil, and combined with a variety of new technology, to complete myocardial comprehensive imaging, which can provide much information, such as myocardial permutation order, collagen fiber content quantization, myocardial mechanical changes, microvascular obstruction, extra cellular volume and so on. Hence, cardiac magnetic resonance imaging can achieve all-round evaluation of heart. Through dynamic observation MRI performance in different stage after myocardial infarction, and meanwhile, contrast with TGF-β1 expression level, histopathological and immunohistochemical results, we can clarify dynamic monitoring ability and value of MRI functional imaging technology in non-infarction myocardium remodeling process，explore pathophysiology mechanism of non-infarction myocardium in the process of ventricular structural reconstruction.

心室重构是心肌梗死后的重要病理变化，梗死区最明显变化是心肌细胞的坏死和瘢痕形成，非梗死心肌（non-infarcted myocardium，NIM）改变包括心肌细胞肥大、凋亡、纤维排列紊乱、血管再生和间质胶原增生等，这些改变最终可导致心力衰竭而死亡，NIM的改变成为新的研究热点。心肌梗死的治疗重点是保护和修复NIM结构和功能。因此，评估NIM重构过程的结构和功能学变化，对治疗计划制定和疗效评估都至关重要。本研究利用配有动物专用线圈的高场强MRI综合功能成像，组合多种新技术，分别对心肌排列秩序、心肌胶原纤维含量、心肌力学改变、微血管阻塞、细胞外容积等进行多方位评估。动态观察心肌梗死后不同进展阶段的MRI表现，同时与TGF-β1的表达水平、组织病理和免疫组织化学的检测结果相对照，阐明MRI功能成像技术在NIM重构过程中动态监测的能力和价值。探讨心室结构性重构过程中NIM的病理生理学机制。

本项目对心肌梗死后心室重构过程中的变化进行了影像学、生物标记物与病理学关系的探讨。建立稳定的心肌梗死模型。规范了MRI扫描序列。通过对动物模型心肌梗死后不同时段的MRI成像，动态观察疾病不同发展阶段的心肌纤维走向、FA及MD等参数的变化。并在相应时间点测定调控因子TGF-β1、Ang-Ⅱ及TSP-1的表达水平。探讨了心肌梗死后不同阶段的梗死中心区、边缘区及非梗死区结构重构的的MRI成像特点，且结合不同区域调控因子的变化，来探讨MRI在心肌梗死后重构过程中的应用价值。阐明了梗死区和边缘区的FA值在术后第1周时均显著下降，之后下降较缓慢，均在第4周时达最低。在术后4周内，梗死区MD呈迅速明显上升趋势而边缘区MD渐进性轻度升高，两者均是在第4周时达高峰。MI后从CIZ向PIZ延展，再到NIZ代偿性重构，平均FA值呈上升趋势，平均MD值呈下降趋势。