毛蕊花糖苷对嘌呤霉素肾病及足细胞损伤模型的疗效研究

The effect of acteoside on puromycin nephropathy and podocyte injury model

目的探讨地黄叶总苷胶囊有效成分毛蕊花糖苷在治疗蛋白尿和保护足细胞中的作用机制。方法本研究通过建立嘌呤霉素大鼠肾病模型，检测尿蛋白、足细胞损伤标志物和电镜下观察足突融合状态探讨毛蕊花糖苷对蛋白尿治疗和对足细胞保护的作用；通过体外建立嘌呤霉素诱导足细胞损伤模型，进行足细胞活力实验、迁移实验、足细胞细胞骨架检测，以及足细胞损伤标志物nephrin检测，探讨毛蕊花糖苷对足细胞保护效应。结果体内研究中，毛蕊花糖苷可以有效地降低嘌呤霉素大鼠蛋白尿水平（P〈0．05），恢复足细胞损伤标志物nephrin、synaptopodin的蛋白表达（均P〈0．05），缓解足细胞足突融合；体外研究中，毛蕊花糖苷可以有效恢复足细胞活力（P〈0．05），降低足细胞受损后增强的迁移能力（P〈0．05），保护足细胞细胞骨架，恢复nephrin蛋白表达（P〈0．05）。结论本研究证实毛蕊花糖苷可以通过保护足细胞降低嘌呤霉素诱导肾病大鼠蛋白尿及缓解嘌呤霉素诱导足细胞损伤，丰富了对地黄叶总苷胶囊降低蛋白尿作用的认识。

Objective To explore the effect of acteoside （one of the ingredients of Total Glycosides Extracted from Rehmannia capsules） on treatment of proteinuria and protection of podocytes. Methods In this study, puromycin nephropathy rat model was successfully established. After detecting the degree of proteinuria, the expression of podocyte injury markers and the degree of podocyte foot process fusion were investigated by electron microscope. In addition, puromycin treated podocyte injury model was also successfully established in vitro. Podocyte viability, migration, cytoskeleton and injury marker were detected. Results In vivo study showed that acteoside could effectively reduce proteinuria （P 〈 0.05）, restore the expression of podocyte injury markers such as nephrin and synaptopodin （all P 〈 0.05）, and alleviate the degree of podocyte foot process fusion. In vitro study showed that acteoside could effectively restored podocyte viability （P 〈 0.05）, reduce abnormal migration ability （P 〈 0.05）, protecte cytoskeleton and restore the expression of podocyte injury marker nephrin （P 〈 0.05）. Conclusions This study confirms that aeteoside can reduce the degree of proteinuria in puromycin nephropathy rat model in vivo and alleviate the degree of podocyte injury in vitro as well as enrich the molecular mechanism of Total Glycosides Extracted from Rehmannia capsules in treatment of proteinuria.