关键词: 糖尿病肾病, 多肽, 线粒体, FUN14结构域蛋白1(FUNDC1), Apelin

Abstract: Objective To explore the protective effect of polypeptide Apelin on podocyte mitochondria in diabetic nephropathy and underling mechanisms. Methods Human renal podocytes were divided into four experimental groups: control group, high glucose(HG) group(glucose 25 mmol/L, 48 h), Apelin intervention HG group (Apelin-13 1 μmol/L, 48 h) and Apelin group (Apelin-13 1 μmol/L, 48 h). The podocyte apoptosis was observed by TUNEL staining, the expression of mitochondrial membrane protein FUNDC1 was detected by Western blot, and the binding of mitochondrial fission protein DRP1 to FUNDC1 was examined by immunoprecipitation. The 8-week-old male mice were divided into three experimental groups: control group, diabetes group (intraperitoneal injection of streptozotocin 150 mg/kg, only one time) and Apelin intervention DM group (intraperitoneal injection of Apelin-13 0.3 μmol/kg, daily). The morphology of renal was observed by PAS staining and transmission electron microscopy. Plasma creatinine (Cr), urea nitrogen, urinary albumin and creatinine were detected by ELISA kit. The level of creatinine clearance rate (Ccr) and urinary albumin/creatinine (ACR) was calculated. Results Compared with the control group, the podocyte apoptosis and expression of FUNDC1 in the HG group increased significantly (P＜0.05), and the combination of mitochondrial fission division protein DRP1 to FUNDC1 raised. Meanwhile, compared with the HG group, the number of apoptosis, the expression of FUNDC1 (P＜0.05), and the combination of DRP1 to FUNDC1 all reduced in Apelin intervention HG group. Animal experiments showed that the kidney structure of the control group was intact. In the DM group, the number of podocytes decreased significantly, the foot processes were fused and dropped off. In the Apelin intervention DM group, podocyte lesions were less severe than those in the DM group. Compared with the control group, the level of plasma Cr, BUN and urine ACR in the DM group increased, while the level of Ccr decreased significantly (P＜0.05). However, compared with the DM group, the level of above biomarkers in the Apelin intervention DM group was improved(P＜0.05).Conclusions Apelin keeps mitochondrial homeostasis and reduces podocyte apoptosis by inhibiting the expression of mitochondrial membrane protein FUNDC1, which may contribute to alleviation of diabetic nephropathy.

Key words: diabetic nephropathy, polypeptide, mitochondrion, FUNDC1, Apelin