依达拉奉对肾缺血再灌注损伤的保护作用

The protection of Edaravone against renal ischemia-reperfusion injury in rats

目的探讨依达拉奉对肾脏缺血再灌注损伤的保护作用。方法将40只雄性Wistar大鼠随机分为假手术组(S组)、缺血再灌注组(I组)、EA组、EB组和EC组,其中除了S组外,其余大鼠均夹闭双侧肾蒂45min、再灌注24h制成肾缺血再灌注损伤动物模型。缺血前和再灌注即刻,EA组、EB组、EC组分别经尾静脉给予依达拉奉1mg/kg、3mg/kg、6mg/kg,S组和I组经尾静脉给予等量生理盐水。于再灌注24 h取股动脉血检测丙二醇(MDA)、超氧化物歧化酶(SOD)、尿素氮(BUN)、肌酐(Cre),取左肾免疫组织化学观察肾脏细胞凋亡。结果(1)EA组、EB组的MDA随依达拉奉剂量增大而降低(P<0.05),但EC组的MDA高于EB组(P<0.05);上述三组的MDA均低于I组(P<0.05)。(2)在SOD活力方面,EA组和I组之间、EB组和EC组之间无显著性差异(P>0.05),但EB组和EC组均高于EA组和I组(P<0.05)。(3)EA组、EB组的BUN、Cre之间比较无显著性差异(P>0.05),但均明显低于I组(P<0.05);而EC组的BUN、Cre与I组比较差异无显著性;(P>0.05)。(4)免疫组织化学显示,I组中肾脏细胞凋亡指数较S组上升,EB组则较I组下降(P<0.05)。结论大鼠肾脏缺血再灌注损伤时,依达拉奉能清除氧自由基、减少肾脏细胞凋亡,对肾脏缺血再灌注损伤具有保护作用。

Objective To investigate the protective effect of Edaravone on rat kidneys with ischemia -reperfusion injury. Methods Forty normal male Wistar rats were divided randomly into 5 groups： sham-operated group （S group）, ischemia-reperfusion group（I group）, EA group, EB group and EC group. All rats, except S group with only anesthetization and leparotomy but not ischemia, were subjected to renal ischemia-reperfusion injury by clamping bilateral renal pedicles for 45 minutes followed by 24th of reperfusion. Rats were treated before and after ischemia with Edaravone to EA group （1mg/kg）, EB group（3mg/kg）, EC group（6mg/kg） or saline to S group and I group, administered by tail vein injection. After the reperfusion period of 24h, the rats were sacrificed and the changes of serum malondialdehyde（MDA）, superoxide dismutase（SOD）, blood urea nitrogen（BUN）, creatinine （CRE） as well as renal cell apoptosis in rat kidneys were observed. Results （1） The levels of MDA in the EA, EB group decreased with dosange of Edaravone increasing （P〈0. 05）, but the levels of MDA in the EC group was higher than that in the EB group（P〈0.05）. All of them significantly lower than that in the I group. （2） The activity of ,SOD in the EB group and the EC group were significantly higher than that in the EA group and the I group（P〈0. 05）, but there were no significant differences in the EB group vs the EC group and the EB group had no difference（P〉0. 05）, but they both were significantly lower than that in the I group（P〈0. 05）, whereas there were no significant difference in the EC group compared with the I group（P〉0. 05）. （4） Immunohistochemical study showed that the index of renal cell apoptosis in rat kidneys in the EB group was significantly decreased than that of the I group（P〈0. 05）. Conclusion Edaravone scavenges oxygen free radicals, decreases renal cell apoptosis and possesses protective effect on kidney with ischemia-reperfusion injury.