PMID- 32606875 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220415 IS - 1178-7007 (Print) IS - 1178-7007 (Electronic) IS - 1178-7007 (Linking) VI - 13 DP - 2020 TI - Activation of Nrf2 Signaling by Apelin Attenuates Renal Ischemia Reperfusion Injury in Diabetic Rats. PG - 2169-2177 LID - 10.2147/DMSO.S246743 [doi] AB - OBJECTIVE: 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-alpha), interleukin 1beta (IL-1beta), 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. CI - (c) 2020 Zhang et al. FAU - Zhang, Xiaobo AU - Zhang X AD - Nephrology Department, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu Province 223300, People's Republic of China. FAU - Zhu, Ying AU - Zhu Y AD - Nephrology Department, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu Province 223300, People's Republic of China. FAU - Zhou, Ying AU - Zhou Y AD - Nephrology Department, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu Province 223300, People's Republic of China. FAU - Fei, Bingru AU - Fei B AD - Nephrology Department, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huaian, Jiangsu Province 223300, People's Republic of China. LA - eng PT - Journal Article DEP - 20200623 PL - New Zealand TA - Diabetes Metab Syndr Obes JT - Diabetes, metabolic syndrome and obesity : targets and therapy JID - 101515585 PMC - PMC7320893 OTO - NOTNLM OT - Apelin OT - Nrf2 signaling OT - diabetes OT - renal ischemia/reperfusion injury COIS- The authors declare that they have no competing interests. EDAT- 2020/07/02 06:00 MHDA- 2020/07/02 06:01 PMCR- 2020/06/23 CRDT- 2020/07/02 06:00 PHST- 2020/01/20 00:00 [received] PHST- 2020/03/23 00:00 [accepted] PHST- 2020/07/02 06:00 [entrez] PHST- 2020/07/02 06:00 [pubmed] PHST- 2020/07/02 06:01 [medline] PHST- 2020/06/23 00:00 [pmc-release] AID - 246743 [pii] AID - 10.2147/DMSO.S246743 [doi] PST - epublish SO - Diabetes Metab Syndr Obes. 2020 Jun 23;13:2169-2177. doi: 10.2147/DMSO.S246743. eCollection 2020.