七氟醚对幼鼠肝缺血再灌注后肾损伤和铁死亡的影响

Effect of Sevoflurane on Renal Injury and Ferroptosis after Hepatic Ischemia-Reperfusion in Young Rats

为了探讨铁死亡在儿童肝移植术后肾损伤的作用及七氟醚对其的影响,本研究选用幼年大鼠70%肝缺血再灌注(Hepatic ischaemia reperfusion,HIR)模型模拟儿童肝移植过程,评估肝缺血再灌注后肾铁死亡程度及七氟醚的影响;并在体外使用Erastin诱导的HK-2肾细胞模型探讨七氟醚对肾细胞铁死亡的直接作用机制.结果表明,在HIR幼鼠模型中,1.3%和2.2%七氟醚可减轻肾脏病理损伤、改善肾功能、抑制炎症反应,1.3%效果优于2.2%;七氟醚可通过降低铁死亡相关蛋白TFRC和ACSL4的表达减轻肾铁死亡,并可降低HIR幼鼠模型的肾脏铁含量、肾组织ROS、MDA水平,增加SOD和GSH水平,1.3%与2.2%浓度作用无差异.在体外实验中,七氟醚可通过降低Erastin诱导的肾HK-2细胞TFRC和ACSL4水平,降低细胞铁含量和ROS水平,缓解肾细胞铁死亡,减轻肾损伤.综上所述,七氟醚通过降低HIR诱导的幼鼠模型铁死亡和Erastin诱导的肾HK-2细胞铁死亡来发挥肾保护作用.七氟醚可能通过缓解肾脏铁死亡,在围术期器官保护方面具有潜在临床应用前景.

To investigate the role of ferroptosis in renal injury after liver transplantation in children and the effect of sevoflurane on it,the present study was conducted in vivo using a70%hepatic ischemia/reperfusion model in juvenile rats to mimic the process of liver transplantation in children,to assess the extent of renal ferroptosis after hepatic ischemia/reperfusion and the effect of sevoflurane,and in vitro using the Erastin-induced HK-2 renal cell model to explore the direct mechanism of the effect of sevoflurane on renal cell ferroptosis.An Erastininduced HK-2 renal cell model in vitro was used to investigate the direct effect of sevoflurane on renal cell ferroptosis.The results showed that 1.3%and 2.2%of sevoflurane could reduce renal pathological injury,improve renal function,and inhibit inflammation in the HIR model,and the effect of 1.3%was better than that of 2.2%.1.3%and 2.2%of sevoflurane could reduce renal ferroptosis by lowering the expression of ferroptosis-related proteins,TFRC and ACSL4,and also reduced renal iron content,renal ROS,and MDA levels,and increased SOD and GSH levels in HIR model,with no difference between 1.3%and 2.2%concentration.In vitro experiments,sevoflurane could alleviate renal cell ferroptosis and reduce renal injury by decreasing the levels of TFRC and ACSL4 in renal HK-2 cells induced by Erastin,decreasing cellular iron content and ROS levels.In conclusion,sevoflurane exerted its nephroprotective effects by decreasing HIR-induced ferroptosis and Erastin-induced ferroptosis in renal HK-2 cells in a young rat model.Sevoflurane may have potential clinical applications in perioperative organ protection by alleviating renal ferroptosis.