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. 2020 Jun 23:13:2169-2177.
doi: 10.2147/DMSO.S246743. eCollection 2020.

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

Xiaobo Zhang  1 , Ying Zhu  1 , Ying Zhou  1 , Bingru Fei  1
Affiliations

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

Xiaobo Zhang et al. Diabetes Metab Syndr Obes. .

Abstract

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-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: Apelin; Nrf2 signaling; diabetes; renal ischemia/reperfusion injury.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Effects of Apelin on the function and histological structure of kidneys. (A) Relative biochemical kits for detection of BUN and SCR levels in the serum of rats in five groups. (B) H&E staining of histopathological changes in five groups of kidney tissues. ***P<0.001 vs Control; ###p<0.001 vs Db; ΔΔΔp<0.001 vs Db+I/R+NC.
Figure 2
Figure 2
Effects of Apelin on inflammatory cytokines and oxidative stress. (A, B) TNF-a, IL-1β, IL-6 and MCP-1 levels were separately estimated via the usage of ELISA and RT-qPCR experiments in the serum and kidney tissues. (C) The expression of ROS was estimated via ROS kits. **p<0.01,***P<0.001 vs control; ###p<0.001 vs Db; ΔΔΔp<0.001 vs Db+I/R+NC.
Figure 3
Figure 3
Impacts of Apelin on the apoptosis. (A) TUNEL assay was utilized to measure cell apoptosis in five groups. (B) Statistical analysis of apoptosis. (C) Western blot assessed the protein levels of apoptosis-related proteins. **p<0.01, ***p<0.001 vs control; #p<0.05, ###p<0.001 vs Db; ΔΔΔp<0.001 vs Db+I/R+NC.
Figure 4
Figure 4
Apelin had a promotive effect on Nrf2 and its downstream genes. Western blot detection of Nrf2, CAT, NQO1, SOD1, GSS, GCLM and GCLC levels under five treatments. **p<0.01, ***p<0.001 vs control; ##p<0.01, ###p<0.001 vs Db; ΔΔΔp<0.001 vs Db+I/R+NC.
Figure 5
Figure 5
Apelin had a promotive effect on Nrf2. IHC analysis of Nrf2 expression changes under five kinds of treatments.
See this image and copyright information in PMC

References

    1. Li M, Ikehara S. Bone marrow stem cell as a potential treatment for diabetes. J Diabetes Res. 2013;2013:329596. doi:10.1155/2013/329596 - DOI - PMC - PubMed
    1. Costa PZ, Soares R. Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox. Life Sci. 2013;92(22):1037–1045. doi:10.1016/j.lfs.2013.04.001 - DOI - PubMed
    1. Rocca B, Rubboli A, Zaccardi F. Antithrombotic therapy and revascularisation strategies in people with diabetes and coronary artery disease. Eur J Prev Cardiol. 2019;26(2_suppl):92–105. doi:10.1177/2047487319880045 - DOI - PubMed
    1. Gao H, Yang Y, Deng J, Liang J, Zhang W, Feng X. A systematic review and meta-analysis on the efficacy and safety of traditional Chinese patent medicine Jinqi Jiangtang Tablet in the treatment of type 2 diabetes. Complement Ther Med. 2019;47:102021. doi:10.1016/j.ctim.2019.01.016 - DOI - PubMed
    1. Palumbo PJ, Elveback LR, Chu C-P, Connolly DC, Kurland LT. Diabetes mellitus: incidence, prevalence, survivorship, and causes of death in Rochester, Minnesota, 1945–1970. Diabetes. 1976;25(7):566–573. doi:10.2337/diab.25.7.566 - DOI - PubMed