Desflurane Preconditioning Protects Against Renal Ischemia–Reperfusion Injury and Inhibits Inflammation and Oxidative Stress in Rats Through Regulating the Nrf2-Keap1-ARE Signaling Pathway

Drug Design, Development and Therapy

关键词: ischemia-reperfusion;    kidney;    animal model;    desflurane;    nrf2-keap1-are signaling pathway;   

DOI  :  

来源: DOAJ

【 摘 要 】

Yan Zheng,1,* Hui Lu,1,* Huiqiong Huang2 1Department of Anesthesiology, Xiamen Haicang Hospital, Xiamen 361000, People’s Republic of China; 2Department of Anesthesiology, Women and Children’s Hospital Affiliated to Xiamen University, Xiamen 361000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Huiqiong HuangDepartment of Anesthesiology, Women and Children’s Hospital Affiliated to Xiamen University, No. 10 Zhenhai Road, Xiamen 361000, People’s Republic of ChinaTel [phone]Email [e-mail]: Kidney is sensitive to ischemia–reperfusion (I/R) injury because of its special structure and function. In this study, we aimed to explore the mechanism of desflurane (DFE) preconditioning effecting on renal I/R injury in rats.Methods: Renal I/R injury rats model was constructed, and the expressions of serum renal function parameters (blood urea nitrogen (BUN) and serum creatinine (SCr)) and lipid peroxidation-related factors were detected using corresponding commercial kits to assess the degrees of renal functional damage and oxidative stress. Hematoxylin–-eosin (HE) staining and Masson trichrome staining were applied to measure the renal histologic damage. The expressions of inflammation-related factors were determined by ELISA assay. The cell apoptosis was analyzed using TUNEL, Western blot and immunohistochemistry (IHC). IHC was also used to detect the number of myeloperoxidase (MPO)-positive cells. The expressions of proteins associated with the Nrf2-Keap1-ARE pathway were assessed by Western blot and IHC.Results: DFE preconditioning inhibited I/R injury-induced BUN and SCr increase and renal histologic injury in rats. Also, DFE suppressed the inflammation, apoptosis and oxidative stress caused by renal I/R injury in vivo. In addition, DFE preconditioning repressed peroxide-related factors (MDA, MPO and NO) expressions and promoted antioxidant-related factors (GSH, SOD, GPx and CAT) expressions. In addition, DFE promoted Nrf2-Keap1-ARE-related proteins including Nrf2, NQO1, HO-1, γ-GCS, GSR and GCLc expressions.Conclusion: DFE preconditioning protected the kidney as well as inhibited the inflammation, cell apoptosis and oxidative stress in renal I/R injury rats by activating the Nrf2-Keap1-ARE signaling pathway.Keywords: ischemia–reperfusion, kidney, animal model, desflurane, Nrf2-Keap1-ARE signaling pathway

【 授权许可】

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