肾病综合征（NS）是造成终末期肾脏衰竭常见原因之一、严重危害人类健康的一类肾脏疾病。课题组前期研究提示血管生成样蛋白3(ANGPTL3)在NS足细胞损伤和蛋白尿发生过程中起重要作用，体内调控ANGPTL3表达的机制尚不清楚。本项目拟在已有工作基础上,通过构建阿霉素肾病模型，首先应用Angptl3-/-小鼠探讨Angptl3全敲对NS转归的影响；继而通过肝细胞特异性Angptl3敲除和足细胞特异性Angptl3敲除小鼠确定是肾源性还是肝源性Angptl3在NS足细胞损伤和蛋白尿发生中起主要作用；进一步通过特异性microRNA和小干扰RNA的干预降低小鼠Angptl3的表达、以观察Angptl3低表达对肾脏的保护作用。以上研究结果将进一步明确ANGPTL3在NS蛋白尿和足细胞损伤中的作用机制，以及对NS转归的重要影响，为新的足细胞保护手段开辟思路，并为今后开发针对性药物提供潜在靶点。

Nephrotic Syndrome(NS) is a collection of signs and symptoms endangering the human health seriously and responsible for approximately 15% of all causes of end-stage renal disease (ESRD). In previous study, we found that ANGPTL3 played an important role in proteinuria and podocyte injury in NS, but the mechanism is unclear. In this project, we will firstly establish adriamycin nephropathy model on Angptl3-/- mice to explore the impact of knockout Angptl3 on the outcome of NS; then develop podocyte-specific(NPHS2-Angptl3, diminish podocyte expression) and hepatocyte-specific (ALB-Angptl3, diminish circulating Angptl3 secreted from hepatocyte tissue) Angptl3-knockout transgenic mice to independently study the effects of increased podocyte expressing or circulating Angptl3 on glomerular function; furthermore, we will use MicroRNAs and interfering RNAs-mediated reduction in Angptl3 mRNA expression to demonstrate reduced Angptl3 expression is associated with the protective effect on NS. This study will further confirm the role of abnormal Angptl3 expression in NS proteinuria and podocyte injury, as well as an important impact on the outcome of NS, opened up ideas for new means of podocyte protection, and provide a potential target for the future development of targeted drugs.