肾病一号方调控足细胞ANGPTL3表达的机制研究

ANGPTL3在足细胞中高表达与足细胞损伤密切相关，ANGPTL3高表达导致足细胞骨架紊乱，活动性增加，尿蛋白增多，敲低足细胞ANGPTL3表达减轻了阿霉素对足细胞的损伤；小鼠体内敲除ANGPTL3不影响肾脏的发育和肾功能，足细胞超微结构正常，显著减轻了阿霉素肾病模型小鼠的足细胞的损伤，有效减少尿蛋白；积极寻求调控ANGPTL3表达的药物对防止或减轻足细胞损伤具有重要意义。肾病一号方在临床和大鼠阿霉素肾病模型中能够有效减少尿蛋白，减轻阿霉素肾病大鼠的足细胞损伤，但肾病一号方在足细胞损伤过程中是否通过调控ANGPTL3表达而起到对足细胞的保护有待进一步研究，课题拟通过肾病一号方在阿霉素肾病模型及体外足细胞损伤研究中深入探索其对足细胞的保护作用与足细胞ANGPTL3表达变化的关系，研究肾病一号方在调控足细胞ANGPTL3表达中的分子机制。

ANGPTL3 over－expression in podocytes is closely related to podocyte injury , ANGPTL3 over－expression led to podocyte skeleton disorders, increased motility, increased urinary protein, while knockdown ANGPTL3 expression in podocytes reduced Adriamycin－induced podocyte injury. Moreover, ANGPTL3 knockout in mice does not affect the development of the kidney and renal function, maintain normal podocyte ultrastructure, significantly reduced podocyte injury in adriamycin-induced nephropathy, decreased urinary protein. It is significantly important to actively discover the drugs of regulation of expression of ANGPTL3 in podocytes for preventing or minimizing podocyte injury, and Shenbing yihao prescription can effectively decrease proteinuria, reduce podocyte injury in clinical and adriamycin-induced nephropathy, but whether the protective role of shenbing yihao prescription in podocyte injury is through the regulation of ANGPTL3 expression in podocytes is needed further study. It is necessary to explore the relationship between the protective effect on podocyte injury and the change of ANGPTL3 expression in podocytes in vivo and in vitro, and further explore the mechanism of shenbing yihao prescription in regulating ANGPTL3 expression in podocytes.