Ｏｂｊｅｃｔｉｖｅ：To investigate whether erythropoietin (EPO) derived peptide ARA290 can inhibit oxidative stress injury of kidney and play a renal protective role in diabetic rats.
Ｍｅｔｈｏｄｏｌｏｇｙ：Diabetic rats were induced by intraperitoneal injection of streptozotocin. Diabetic rats were randomly divided into diabetic model group,ARA290 50 U/kg treatment group,ARA290 100 U/kg treatment group,and normal control group was set up at the same time. After 12 weeks of drug intervention,urinary albumin/creatinine (ACR) and β2microglobulin (β2MG) were measured. The pathological changes of kidney were observed by PAS staining. The expressions of EPO receptor (EPOR) and CD131 in rat kidney were detected by immunofluorescence and coimmunoprecipitation. The expression of NOX4 in rat kidney was detected by quantitative realtime PCR and western bloting. The ROS level in rat kidney was detected by ELISA. The expressions of malondialdehyde (MDA) and 8 hydroxydeoxyguanosine (8OHdG) in rat kidney were detected by immunohistochemistry.
Ｒｅｓｕｌｔｓ：ARA290 could reduce ACR and β2MG in diabetic rat urine. Immunofluorescence assay showed that EPOR and CD131 were expressed in rat kidneys,and they were colocalized; coimmunoprecipitation showed that EPOR and CD131 were interlinked in the kidney; ARA290 could alleviate renal pathological damage,inhibit the expression of NOX4,reduce ROS level,and decrease expressions of MDA and 8OHdG in the kidney of diabetic rats.
Ｃｏｎｃｌｕｓｉｏｎ：EPOR and CD131 are expressed in rat kidneys,and they bind to each other in kidney. ARA290 inhibit oxidative stress injury,plays a renal protective role in diabetic rats,which might be mediated by EPORCD131 protein complex.