Activation of Nrf2 Signaling by Apelin Attenuates Renal Ischemia Reperfusion Injury in Diabetic Rats.

Abstract

ObjectiveRenal ischemia/reperfusion (I/R) injury is commonly seen in diabetic patients. Apelin has been demonstrated to protect against renal I/R injury, whereas detailed modulatory mechanisms by which Apelin exerts its role in renal I/R injury in diabetic patients remain unclarified. This research aimed to probe the functional molecules under the regulation of Apelin in renal I/R injury in diabetic rats.Materials and MethodsFirst, animal models were established for subsequent assays. Biochemical kits measured the serum levels of blood urea nitrogen (BUN) and serum creatinine (SCR), and hematoxylin and eosin (H&E) staining examined the histopathological changes of kidney tissues. Inflammatory factors containing tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), interleukin 6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) were tested through enzyme-linked immunosorbent assay (ELISA) and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. Reactive oxygen species (ROS) levels in the serum and kidney tissues were separately assessed by specific ROS kits. Cell apoptosis was further estimated through terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and Western blot analysis. Eventually, the influences of Apelin on nuclear factor erythroid 2-related factor (Nrf2) and its downstream genes were explored via Western blot analysis and immunohistochemistry (IHC).ResultsIn the present study, Apelin ameliorated the damage to renal function and histological structure, decreased levels of inflammatory factors and ROS, and hampered cell apoptosis in renal I/R injury of diabetic rats. Moreover, Apelin could elevate the levels of Nrf2 and downstream genes which were decreased under renal I/R injury.ConclusionThese data indicated that Apelin inhibited renal I/R injury through regulating Nrf2 signaling in diabetic rats, which might shed new light on the treatment of renal I/R injury in diabetic patients.