七氟醚预处理在肾缺血再灌注中的保护作用

Protective effect and mechanism of sevoflurane preconditioning on renal ischemia reperfusion injury

目的:探讨七氟醚(Sev)预处理减轻肾缺血再灌注损伤的作用与HIF-2α表达的关系。方法:将野生型(WT)小鼠和HIF-2α基因敲除(HIF-2α-/-)小鼠随机分为假手术组(Control组)、肾缺血再灌注组(I/R组)和Sev预处理+肾缺血再灌注组(I/R+Sev组)。建立肾缺血再灌注模型后检测肾血流量、血尿素氮(BUN)和肌酐(Cr)的水平,TUNEL法检测肾脏细胞凋亡,Western blotting检测肾组织HIF-2α水平。结果:WT小鼠中I/R+Sev组的血BUN和Cr水平显著低于I/R组(P<0.001)、肾相对血流量显著高于I/R组(P<0.05)、细胞凋亡数明显少于I/R组(P<0.05),而HIF-2α-/-小鼠中I/R组和I/R+Sev组的这些监测指标都没有统计学差异。WT小鼠中I/R+Sev组的HIF-2α蛋白水平显著高于I/R组(P<0.05)。结论 :Sev预处理可能通过增加HIF-2α表达的稳定性,从而抑制细胞凋亡、改善肾功能,达到肾保护作用。

Objective To explore the renal protective effect of sevoflurane （Sev） preconditioning on re- nal ischemia reperfusion injury and its relationship with the expression of HIF-2a. Methods Wild type （WT） mice and HIF-2a knockout mice （HIF-2a） were randomly divided into control group （sham operation）, I/R group （renal ischemia/reperfusion group） and I/R ＋ Sev group（sevoflurane preconditioning before renal ischemi- a/reperfusion）. Levels of blood urea nitrogen （BUN） and serum creatinine （Cr）, renal blood flow and apoptotic cells by TUNEL were monitored. Expression of renal HIF-2a was exa mined by western blotting. Results In WT mice, blood BUN and Cr levels and the number of apoptotic cells of I/R ＋ Sev group decreased significantly compared with those of I/R group （P 〈 0.001 ）. Renal blood flow of I/R ＋ Sev group was significantly higher than that of I/R group in WT mice （P 〈 0.05）. There were no significant differences of above-mentioned indica- tors between I/R group and I/R ＋ Sev group in HIF-2a-/- mice. Renal HIF-2a expression levels were signifi- cantly higher in I/R ＋ Sev group than those in control group and I/R group. Conclusion Sev preconditioning could increase the expression of HIF-2a, thus inhibit cell apoptosis and improve renal function and alleviate re- nal ischemia reperfusion injury.