目的:研究NPHS1两种新突变编码蛋白在细胞内的分布与先天性肾病综合征发病机制的关系。方法:构建野生型和两种突变型NPHS1克隆,并转染至COS7细胞内,应用免疫荧光双标记的方法,分别进行细胞内及细胞表面的荧光标记,通过共聚焦显微镜对裂隙膜分子Nephrin在细胞内的分布进行研究。结果:野生型Nephrin表现为细胞内和细胞膜染色模式;V822M和C265R则主要为细胞内内质网染色模式,细胞膜着色几乎缺失。结论:突变的Nephrin蛋白由于错误折叠,不能由内质网被输送至细胞表面,这可能是先天性肾病综合征发病的机制之一。 OBJECTIVE: To study the relationship between the intracellular distribution of NPHS1 two novel mutations and the pathogenesis of congenital nephrotic syndrome. Methods: Wild-type and two mutant NPHS1 clones were constructed and transfected into COS7 cells. Fluorescent labeling was performed on both intracellular and cell surface by immunofluorescence double labeling. The expression of Nephrin Intracellular distribution was studied. Results: The expression of wild-type Nephrin showed intracellular and cell membrane staining patterns. V822M and C265R were mainly intracellular endoplasmic reticulum staining patterns with almost no cell membrane staining. Conclusion: The mutated Nephrin protein can not be transported to the cell surface by endoplasmic reticulum due to misfolding, which may be one of the mechanisms of congenital nephrotic syndrome.