基于"脂肪-内皮祖细胞-血管通透性"机制的糖尿病骨髓微血管病变MRI定量和纹理分析研究

The relationship among temporal changes and regulation mechanisms of bone marrow adipose content, fatty acid composition, mobilization of endothelial progenitor cells (EPCs) and vessel permeability change interactively in earlier diabetic bone marrow microangiopathy is still unclear and need to be explored. In the early experiment,we found that microvascular permeability and fat content of the bone marrow increased significantly ,meanwhile bone marrow osteoblast microenvironment damage.In the present study, we will evaluate correlation between the bone marrow blood perfusion, vessel permeability and lipid water content on the ALX induced diabetic rabbit model by IDEAL-IQ and DCE-MRI in vivo at 3.0 Tesla, and assess the ultrastructural of bone marrow with texture analysis. Meanwhile, we will demonstrate the hypothesis that the fatty acid composition reduced vessel permeability, EPCs in earlier diabetic bone marrow as well as mobilization of EPCs by 1H HRMAS NMRS and flow cytometry. This is the first study that reveal mechanisms of adipose tissue and endothelial progenitor cells- mediated vessel permeability changes in earlier diabetic bone marrow microangiopathy in vivo and in vitro by quantitative MRI. These results provide a new imaging research approach for the pathophysiology of earlier diabetic bone marrow microangiopathy, which is also providing powerful theoretical basis for preventing adipogenesis, promoting mobilization of EPCs and interfering with angiogenesis in earlier treatment of diabetic bone marrow microangiopathy.

骨髓脂肪、内皮祖细胞动员以及骨髓血管通透性在早期糖尿病骨髓微血管病变发生、进展过程的时序变化及调控机制仍是未知的研究领域。申请人前期实验研究发现骨髓微血管通透性及脂肪含量明显增加，骨髓成骨细胞微环境破坏。本项目采用IDEAL-IQ评价四氧嘧啶糖尿病兔模型的骨髓脂肪含量，同时采用DCE-MRI的定量参数评价早期糖尿病骨髓微血管的灌注和通透性特征，并利用放射组学纹理分析技术评价早期骨髓超微结构。采用离体骨髓组织氢质子高分辨魔角旋转磁共振波谱和流式细胞仪探索骨髓脂肪酸成分在早期糖尿病骨髓内皮祖细胞动员及微血管病变的发生、发展中的变化规律。采用定量MRI首次从活体和离体层面揭示早期糖尿病骨髓微血管病变“脂肪-内皮祖细胞-血管通透性”调控机制，为糖尿病骨髓微血管病变的病理生理机制提供新的影像学研究思路，并为糖尿病骨髓微血管病变早期成脂干预、促内皮祖细胞动员和干预血管生成治疗提供有力的理论依据。

骨髓脂肪、内皮祖细胞动员以及骨髓血管通透性在早期糖尿病骨髓微血管病变发生、进展过程的时序变化及调控机制仍是未知的研究领域。本项目采用IDEAL-IQ评价四氧嘧啶糖尿病兔模型的骨髓脂肪含量，同时采用DCE-MRI的定量参数评价早期糖尿病骨髓微血管的灌注和通透性特征，并利用放射组学纹理分析技术评价早期骨髓超微结构。采用离体骨髓组织氢质子高分辨魔角旋转磁共振波谱和流式细胞仪探索骨髓脂肪酸成分在早期糖尿病骨髓内皮祖细胞动员及微血管病变的发生、发展中的变化规律。研究结果发现1）DCE-MRI定量渗透性参数可以评价糖尿病兔早期骨髓微血管渗透性改变，基于DCE-MRI Ktrans图的纹理参数可识别糖尿病早期骨髓细微结构变化；2）糖尿病早期骨髓微血管病变与脂质代谢有关，主要与亚油酸代谢通路异常有关，IDEAL-IQ和影像组学、代谢组学整合研究评价糖尿病早期骨髓微血管病变方法有待进一步探索；3）DCE-MRI定量参数可以评价维生素D干预四氧嘧啶诱导兔糖尿病模型腰椎骨髓微血管渗透性变化及血流灌注改变，维生素D干预16周内，骨髓微血管Ktrans、Kep值呈下降趋势；4）IDEAL-IQ评价维生素D干预四氧嘧啶诱导兔糖尿病骨髓脂肪含量变化是可行的；维生素D干预16周内，骨髓脂肪含量改变呈现下降趋势；5）IDEAL-IQ联合Micro-CT可以评价四氧嘧啶诱导兔糖尿病早期腰椎骨髓脂肪含量和骨小梁微结构变化，多模态定量影像技术提供了更加全面的骨髓微环境评估手段。