关键词: 香豆素苷, PI3K/ AKT/ mTOR 通路, 糖尿病肾病大鼠, 足细胞损伤

Abstract: Objective To explore the protective effect of coumarin glycosides on podocyte injury by regulating phosphoinositide 3-kinase (PI3K) -protein kinase B (AKT) -mammalian target of rapamycin (mTOR) signaling pathway in rats with diabetic nephropathy. Methods The rat model of diabetic nephropathy was constructed by intraperitoneal injection of streptozotocin ( STZ), and different doses of coumarin glycosides extracted from hydrangea paniculata ( HP), were used to treat the rat model of diabetic nephropathy. Blood glucose, urine protein and endogenous creatinine clearance rate in rats were measured. Immunohistochemistry (IHC) was applied to detect the apoptosis of podocytes in rats. Real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression levels of podocyte split membrane proteins Nephrin, Prodocin, and Desmin, a podocyte injury marker. Western blotting was adopted to detect the expression levels of proteins in PI3K/ AKT / mTOR signaling pathway and their phosphorylation. Results HP could significantly improve the renal function in the rat model. In the model group relative to the control group, the expression levels of fibronectin and type Ⅳ collagen were significantly increased, and the expression levels of Nephrin and Prodocin were significantly downregulated while the expression of Desmin was significantly up-regulated, and the phosphorylation level of PI3K/ AKT / mTOR was decreased significantly (P < 0. 05). With the dose of HP treatment increased, the expression levels of fibronectin and type Ⅳ collagen were decreased, and the expression levels of Nephrin and Prodocin were up-regulated while the expression of Desmin was downregulated in a HP dose-dependent manner, and the PI3K/ AKT / mTOR signaling pathways were significantly activated (P< 0. 05) when compared to the model group. Conclusion Coumarin glycosides can reduce the podocyte injury in rats with diabetic nephropathy by activating the PI3K/ AKT / mTOR signaling pathway.

Key words: coumarin glycosides, PI3K/ AKT / mTOR pathways, rats with diabetic nephropathy, podocyte injury