Effects Of 1,2-dimethanesulfonate Preconditioning On Renal Ischemia/reperfusion Injury In Male Rats

Objective:To investigate the effects of ethane 1,2-dimethanesulfonate(EDS) preconditioning on renal ischemia/reperfusion(I/R) injury in male Sprague Dawley rats.Method:1. The renal pedicles were bilaterally occluded with a microvascular clamp for 45 min to establish renal ischemia-reperfusion-induced injury model.2. Male SD rats(n=48) were randomly assigned to 6 groups: Blank, Sham, I/R, EDS+I/R,EDS+ testosterone(TST) +I/R, castration(Cast)+I/R. Bilateral orchiectomy was conducted 2weeks before surgery.3. EDS(75 mg/kg) was intraperitoneal injected 5 d before operation. Blood samples were collected 24 h after reperfusion from the vena orbitalis posterior plexus.4. Luteinizing hormone(LH), TST, serum creatinine(Scr), blood urea nitrogen(BUN), and kidney injury molecule-1(KIM-1) were detected. Renal and testicle tissues were harvested to assess the kidney morphology, and the level of TNF-α and expression of Fas mRNA and caspase-3 protein of renal tissues were detected.Results:1. Serum T levels in EDS+I/R group and Cast+I/R group were below the minimum detectable dose. After reperfusion, the levels of TST and LH of I/R group were decreased, and TST level of EDS+TST+I/R group was lower than I/R group(P<0.05).2. 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).3. The TNF-α level of I/R group was the highest(P<0.05). Compared with Cast+I/R and EDS+I/R groups, EDS+TST+I/R had a higher TNF-α level(P<0.05).4. Compared with Cast+I/R and I/R group, the expression of Fas mRNA and caspase-3were significantly lower in EDS+I/R group(P<0.05).Conclusion:1. Testosterone can aggravate the kidney ischemia-reperfusion injury. The increase of TNF-α induced by testosterone may be participated.2. EDS preconditioning substantially reduces serum testosterone level, and had a equal effect compared with castration.3. EDS preconditioning could attenuate ischemia-reperfusion-induced acute renal injury and had better renal protection effectiveness compared with castration. Fas/FasL pathway may be involved.4. Testosterone level was decreased during the ischemia-reperfusion process, possible caused by inhibition of LH secretion.