关键词: 阿霉素肾病, 肾小球足细胞, 脂肪细胞膜相关蛋白质(APMAP), NF-κB信号通路

Abstract: Objective To investigate the effects of adipocyte plasma membrane-associated protein (APMAP) over-expression on glomerular podocyte injury in adriamycin (ADR) nephropathy. Methods The rat model of adriamycin nephropathy was constructed by tail vein injection of adriamycin, the expression of APMAP and NF-κB p65 in renal tissue was measured by immunohistochemistry. A mouse glomerular podocytes MPC-5 cell line with APMAP gene over-expression was constructed, then podocyocytes injury model was induced by 0.5 μmol/L ADR and treated with NF-κB signaling pathway activator CU-T12-9. The proliferation of cells was checked by CCK-8. The activity of lactate dehydrogenase (LDH) was determined by ELISA. The apoptosis of podocytes was determined by flow cytometry. Western blot was used to detect protein expressions of NF-κB p65, p-NF-κB p65 and TNF-α. Results APMAP was expressed in kidney tissue of doxorubicin nephropathy rats at a low level, while NF-κB p65 was significantly high expressed (P＜0.05). Over-expression of APMAP increased proliferation of MPC-5 cells and decreased LDH activity, apoptosis rate, and also down-regulated protein expression of NF-κB p65, P-NF-κB p65 and TNF-α under ADR exposure (P＜0.05). However, combined treatment with CU-T12-9 significantly inhibited the ameliorative effect of APMAP over-expression on the damage of MPC-5 cells exposed to ADR. Conclusions The over-expression of APMAP can inhibit ADR-induced glomerular podocyte injury, and its mechanism might be related to the inhibition of NF-κB signaling pathway.

Key words: adriamycin nephropathy, glomerular podocytes, adipocyte plasma membrane-associated protein(APMAP), NF-κB signaling pathway