去铁胺对缺血性急性肾衰竭大鼠的保护作用

Protective Effect of Deferoxamine on Ischemic Acute Renal Failure Rats

目的:探讨去铁胺(DFO)对缺血性急性肾衰竭(iARF)大鼠的保护作用及其作用机制。方法:雄性Wistar大鼠,随机分成3组:假手术组、手术组、DFO+手术组,每组各12只。用钳夹大鼠双侧肾蒂45min制成iARF动物模型,DFO+手术组:缺血前24h给予DFO(200mg/kg)腹腔注射,其余处理同手术组。于缺血再灌注24h后检测血尿素氮(BUN)、肌酐(Scr)、超氧化物歧化酶(SOD)、丙二醛(MDA)的含量以及进行肾组织光镜形态学观察和采用免疫组织化学法测定低氧诱导因子-1α(HIF-1α)及血红素加氧酶(HO-1)蛋白的表达水平。结果:手术组BUN、Scr升高,SOD下降,MDA升高,HIF-1α、HO-1中度提高,肾组织结构紊乱。DFO+手术组除HIF-1α、HO-1含量大幅提高外,尚能显著逆转上述改变,两组间比较具有统计学意义(P<0.01)。结论:DFO预处理可通过自由基清除和诱导HIF-1及下游基因HO-1过表达从而对iARF大鼠发挥保护作用。

Objective： To study the protective effects on and mechanism of deferoxamine （DFO）in ischemic acute renal failure（iARF） rats. Methods：Thirty-six male Wistar rats were randomly divided into three groups with 12 in each group. Rats were assigned into sham, surgery and DFO ＋ surgery groups. Ischernic acute renal failure model was established by bilateral clipping of renal arteries for 45 min and reperfusion for 24 hours. In DFO＋ surgery group,DFO was injected （200 mg/kg IP）24 h before 45 min renal ischemia, the other procedures were the same as those in group model. Activity of superoxide dismutase （,SOD） and content of malondialdehyde （MDA）, blood urea nitrogen （BUN）, serum creatinine （Scr） were examined. Renal structure was evaluated under light microscope. The expressions of HIF-la and HO-1 were detected by immunohistochemistry. Results：Twenty-four hours after reperfnsion, the levels of BUN and Scr and content of MDA were significantly higher in the surgery group than those in the sham group. SOD was just on the opposite. The levels of HIF-la and HO-1 protein in the surgery group were higher than those in the sham groups（P 〈 0.01 ）. DFO ＋ surgery group except HIF - 1 alpha, HO - 1 in substantial increase, may still marked downtum in the above changes, difference between the two groups was significant （P〈 0.01 ）. Conclusion： DFO pretreatment can play on the protective effect of iARF rats by free radical scavenging and the over-expression of hypoxia inducible factor-la and l-hemeoxygenase -1.