超声心动图评价Klotho蛋白在慢性肾脏病左室心肌损伤中的作用研究

慢性肾病（CKD）可导致多种心血管功能障碍，其中心力衰竭是CKD患者常见的并发症和最主要的死亡原因，但导致CKD患者发生左室心肌损伤的确切机制尚未完全阐明。我们前期研究发现超声斑点追踪技术是有效识别心肌损伤的重要方法。新进研究表明Klotho蛋白参与氧化应激、组织纤维化、细胞肥大、内皮功能障碍的发生，且Klotho蛋白在CKD心肌组织中低表达，这提示Klotho蛋白可能成为心室重构防治的新靶点。为此我们推测CKD中Klotho蛋白减低是促使左室重构及功能恶化的重要原因，补充Klotho蛋白可能成为改善左室心肌损伤的有效治疗方法之一。因此本课题拟采用超声心动图及分层斑点追踪技术评价CKD患者Klotho蛋白改变对左室心肌重构及机械力学的影响，并探索左室整体及分层力学改变与Klotho、血液生化指标及心肌病理组织的相关性，为早期评价CKD左室心肌损伤提供新的影像学依据。

Chronic kidney disease (CKD) can cause a variety of cardiovascular dysfunction, of which heart failure is a common complication and the leading cause of death. However, the exact mechanisms underlying the left ventricular myocardial injury in CKD patients has not been fully elucidated. Our previous study found that the speckle-tracking imaging was an important method to effectively identify the myocardial injury. Recent research demonstrated that Klotho protein was involved in the pathogenesis of oxidative stress, fibrosis, cell hypertrophy and endothelial dysfunction, and its expression in myocardium of CKD patients was decreased, which suggested that Klotho protein may be a new target for prevention and treatment of ventricular remodeling. Accordingly, we hypothesized that the decrease of Klotho protein in CKD patients is an important reason for the deterioration of left ventricular remodeling and function, and the increased expression of Klotho protein may be one of the effective treatments to improve the left ventricular myocardial injury. Therefore, the purpose of this study is to evaluate the effects of Klotho protein on the left ventricular remodeling and mechanics by the layer-specific speckle-tracking echocardiography, and to explore the association between the global or layer-specific strain parameters and the changes of Klotho protein, biochemical indexes and myocardial histopathology, which will provide a new imaging evidence for the for earlier detection of left ventricular myocardial injury in CKD patients.