磁共振组织特征成像分析铁超载在糖尿病心肌病心肌纤维化演进中的作用

Myocardial fibrosis is closely related to cardiac dysfunction in patients with diabetic cardiomyopathy and advanced disease may lead to refractory heart failure. Recent studies have found that oxidative stress induced by myocardial iron overload may be the initiating factor of myocardial fibrosis. Our previous study confirmed that the extracellular volume (ECV), a magnetic resonance parameter that reflects the progression of myocardial fibrosis, was increased with the prolongation of clinical course of diabetes, with a good consistency with the pathology of the disease. However, another parameter, the initial T1 value, was not increased, which was presumably related to the reduction effect of iron overload on the T1 value. The initial T1 value is not specific to the detection of iron overload, so it is difficult to explain the logistic relationship between the initial T1 value and the progression of myocardial fibrosis. Based on the previously established diabetic rabbit model, it was designed in the present study to dynamically observe the temporal relation between the iron overload and the production of oxygen free radicals in situ by joint T1 and T2* mapping; and to investigate the distribution of oxygen free radicals and the dynamic change of myocardial fibrosis as well as the dose-response relationship between them, so as to explore the role and status of iron overload in the progression of myocardial fibrosis, providing a continuous and dynamic evaluation method for the clarification of the role of iron overload in the pathogenesis of myocardial fibrosis in diabetic cardiomyopathy, a noninvasive imaging marker in the prediction of cardiac dysfunction caused by myocardial fibrosis, and a theoretical basis for the approaches and time windows of potential early interventions.

糖尿病心肌病中心肌纤维化与心功能障碍密切相关，晚期可引起难治性心衰。近期研究发现由心肌铁超载催化产生的氧化应激反应可能为心肌纤维化的始发因素。我们前期研究证实反映心肌纤维化的磁共振参数细胞外容积分数随着糖尿病病程的延长而增加，且与病理学有很好的一致性，但另一参数初始T1值却并不升高，推测与铁超载降低T1值有关。而初始T1值对铁超载的检测并不特异，难以阐释其与心肌纤维化发展的因果关系。本项目拟在前期建立的糖尿病兔模型基础上，联合T1mapping及T2*mapping技术，在体动态观察铁超载与氧自由基产生的时序关系；分析氧自由基的活化分布与心肌纤维化的量效关系，从而探索铁超载在心肌纤维化演进中的作用和地位。本研究将为阐明铁超载在糖尿病心肌病心肌纤维化发生机制中的作用提供一种连续动态评价方法，为预测心肌纤维化所引起的心功能障碍提供无创影像标志物，并对可能的早期干预方式及干预时间窗提供理论基础。

糖尿病心肌病是指独立于冠状动脉疾病，由高糖血症及胰岛素抵抗诱导，引起心肌纤维化并最终导致心力衰竭的并发症。一旦患者进展到心力衰竭，则心脏的结构和功能将发生不可逆的改变，此时再运用各种治疗方法效果都不佳，如果能对糖尿病心肌病患者进行早期诊断，并及时进行干预，有助于改善患者的预后。而心肌铁超载催化产生的氧化应激反应可能为心肌纤维化的始发因素。本研究通过动物实验及临床试验，联合T1mapping及T2*mapping技术，观察糖尿病心肌铁沉积情况，并分析铁沉积与心肌纤维化及心功能的相关性。结果显示，动物实验中，部分糖尿病兔存在心肌铁沉积及心肌纤维化，但两者之间并不存在必然联系；临床试验中，部分糖尿病患者T2*值明显下降（p＜0.05），表明存在心肌铁沉积，且此类患者心功能减低，证实心肌铁沉积会导致心功能的下降，而此类糖尿病患者整体ECV水平更高（p＜0.05），表明糖尿病患者存在心肌纤维化。因此，本研究为预测心肌纤维化所引起的心功能障碍提供了一种无创的影像标志物，并对可能的早期干预方式及干预时间窗提供理论基础。