Diabetes, Metabolic Syndrome and Obesity (Jun 2020)

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

  • Zhang X,
  • Zhu Y,
  • Zhou Y,
  • Fei B

Journal volume & issue
Vol. Volume 13
pp. 2169 – 2177

Abstract

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Xiaobo Zhang, Ying Zhu, Ying Zhou, Bingru Fei Nephrology Department, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, Jiangsu Province 223300, People’s Republic of ChinaCorrespondence: Xiaobo ZhangThe Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Number 1 Huanghe Xi Lu, Huaiyin District, Huaian, Jiangsu Province 223300, People’s Republic of ChinaEmail [email protected]: Renal 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 Methods: First, 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).Results: In 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.Conclusion: These 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.Keywords: renal ischemia/reperfusion injury, diabetes, Apelin, Nrf2 signaling

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