1,2-二甲磺酸乙烷预处理对雄性SD大鼠肾脏缺血再灌注损伤的影响

目的:探究1,2-二甲磺酸乙烷(EDS)预处理是否对雄性SD大鼠缺血再灌注肾脏损伤有保护作用及其可能机制。方法:夹闭双侧肾蒂45 min,构建雄性SD大鼠肾脏缺血再灌注模型;48只雄性SD大鼠随机分为6组:空白对照组(blank)、假手术组(sham)、肾脏缺血再灌注组(I/R)、EDS预处理+肾缺血再灌注组(EDS+I/R)、EDS预处理+睾酮+肾缺血再灌注组(EDS+TST+I/R)和阉割+肾缺血再灌注组(Cast+I/R)。术前1 h及再灌注后24 h采血检测血清黄体生成素、睾酮、血肌酐、血尿素氮以及尿液肾损伤分子1(KIM-1)水平;取肾脏组织,检测TNF-α水平、Fas mRNA与caspase-3蛋白表达情况。结果:(1)EDS+I/R与Cast+I/R组比较,血肌酐和尿素氮无显著差异(P0.05),但KIM-1水平却低于Cast+I/R组(P0.05),2组血肌酐、血尿素氮和KIM-1均高于另外3组(P0.05)。(2)与术前1 h相比,再灌注术后24 h,EDS+I/R、Cast+I/R及EDS+TST+I/R组均伴睾酮及黄体生成素下降(P0.05)。(3)EDS+I/R组TNF-α水平、Fas mRNA及caspase-3蛋白表达水平均显著低于Cast+I/R与I/R组(P0.05)。结论:EDS预处理可大幅降低血清睾酮水平,从而减轻雄性SD大鼠肾脏缺血再灌注损伤,其机制可能与TNF-α介导的Fas/Fas L通路有关。

Effects of ethane 1,2-dimethanesulfonate preconditioning on renal ische-mia/reperfusion injury in male rats

AIM: To investigate the effects of ethane 1,2-dimethanesulfonate (EDS) preconditioning on renal ischemia/reperfusion (I/R) injury in male Sprague-Dawley (SD) rats. METHODS: Male SD rats (n=48) were randomly assigned to 6 groups: blank, sham, I/R, EDS+I/R, EDS+testosterone (TST)+I/R, and castration (Cast)+I/R. The renal pedicles were bilaterally occluded with a microvascular clamp for 45 min to establish renal I/R-induced injury model. Bilateral orchiectomy was conducted 2 weeks before surgery. EDS (75 mg/kg) was intraperitoneally injected 5 d before operation. Blood samples were collected 24 h after reperfusion from the vena orbitalis posterior plexus. Luteinizing hormone (LH), TST, serum creatinine (SCr), blood urea nitrogen (BUN), and kidney injury molecule-1 (KIM-1) were detected. The renal tissues were harvested to measure the level of TNF-α and the expression of Fas mRNA and caspase-3 protein. RESULTS: Serum TST levels in EDS+I/R group and Cast+I/R group were below the minimum detectable threshold. Compared with other groups, the rats in EDS+I/R group and Cast+I/R group had higher levels of SCr, BUN and KIM-1 (P<0.05). SCr and BUN levels showed no significant difference between EDS+I/R group and Cast+I/R group (P>0.05), but KIM-1 level in EDS+I/R group was lower than that in Cast+I/R group (P<0.05). After reperfusion for 24 h, the levels of TST and LH in EDS+I/R group, Cast+I/R group and EDS+TST+I/R group were lower than those 1 h before operation (P<0.05). Compared with Cast+I/R and I/R group, the TNF-α level and expression of Fas mRNA and caspase-3 protein were significantly decreased in EDS+I/R group (P<0.05). CONCLUSION: EDS preconditioning substantially reduces the serum TST level, thus attenuating I/R-induced acute renal injury. TNF-α-induced Fas/FasL pathway may be involved in this process.