Wang Wen-Xi, Zhao Zhen-Ru, Bai Ying, Li Ya-Xing, Gao Xiao-Ning, Zhang Sen, Sun Yan-Bin
Department of Anesthesiology, Chengde Central Hospital, Chengde, Hebei 067000, P.R. China.
State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, P.R. China.
Exp Ther Med. 2022 Apr;23(4):303. doi: 10.3892/etm.2022.11232. Epub 2022 Feb 22.
Oxidative stress, caused by renal ischemia reperfusion (IR)/hypoperfusion, is one of the main causes of acute kidney injury (AKI). Previous studies have demonstrated that sevoflurane (SEV) protects organs from the damage caused by oxidative stress. In the present study, mice were randomly assigned to a sham operation group (Sham), IR-vehicle group (IR+ vehicle), IR + SEV low-dose preconditioning group and an IR + SEV high-dose preconditioning group. The effect of SEV on nuclear factor E2-related factor 2 (Nrf2), a key regulatory protein of the endogenous antioxidant defense system and, consequently oxidative stress, inflammation and apoptosis-related factors, were all quantified using commercial kits or by western blotting. SEV preconditioning was demonstrated to ameliorate kidney injury as a result of decreased blood urine nitrogen and serum creatinine levels, activated Nrf2 expression in the kidney and decreased oxidative stress and inflammatory index levels an AKI mouse model. SEV preconditioning also protected injured kidney via the downregulation of caspase-3 protein expression levels. In addition, using the Nrf2 inhibitor, Brusatol, significantly abolished the SEV preconditioning renal protective effect. Using an HK-2 cell model of hypoxia/reoxygenation, it was also demonstrated that Nrf2 pathway activation was necessary for SEV to exert its beneficial effect for tubular cell injury caused by hypoxia/reoxygenation. These results indicated that SEV may protect against renal injury caused by IR via Nrf2 upregulation.
由肾脏缺血再灌注（IR）/低灌注引起的氧化应激是急性肾损伤（AKI）的主要原因之一。先前的研究表明，七氟醚（SEV）可保护器官免受氧化应激造成的损伤。在本研究中，将小鼠随机分为假手术组（Sham）、IR-溶剂组（IR+溶剂）、IR + SEV低剂量预处理组和IR + SEV高剂量预处理组。使用商用试剂盒或通过蛋白质免疫印迹法对SEV对内源性抗氧化防御系统的关键调节蛋白核因子E2相关因子2（Nrf2）以及氧化应激、炎症和凋亡相关因子的影响进行了定量分析。在AKI小鼠模型中，SEV预处理可降低血尿素氮和血清肌酐水平，从而改善肾损伤，激活肾脏中Nrf2的表达，并降低氧化应激和炎症指标水平。SEV预处理还通过下调caspase-3蛋白表达水平来保护受损肾脏。此外，使用Nrf2抑制剂布罗索尤单抗可显著消除SEV预处理的肾脏保护作用。利用缺氧/复氧的HK-2细胞模型还证明，Nrf2信号通路的激活是SEV对缺氧/复氧引起的肾小管细胞损伤发挥有益作用所必需的。这些结果表明，SEV可能通过上调Nrf2来预防IR引起的肾损伤。
