HO-1抗大鼠肾缺血/再灌注损伤的实验研究

Protective effect of heme oxygenase-1 against renal ischemia-reperfusion injury in rats

目的探讨诱导血红素氧合酶-1(HO-1)表达能否减轻随后的肾缺血/再灌注损伤(IRI)及其可能的机制。方法采用切除右肾,夹闭左肾动脉50min/再灌注24h的动物模型,30只雄性Wistar大鼠随机均分为3组:假手术组,缺血/再灌注(I/R)组,血晶素处理组(皮下注射血晶素30mg/(kg·d),连续2d),检测肾组织中HO-1蛋白表达及HO-1活力、丙二醛(MDA)含量、总抗氧化能力(TAOC)和血清肌酐(Cr)、尿素氮(BUN)含量及组织形态学改变。结果血晶素明显诱导了肾内HO-1表达并使其活力增加,与I/R组比较,P<0.01;与假手术组比较,I/R组Cr,BUN,MDA升高(P<0.05),TAOC降低(P<0.05),组织学损伤严重。在I/R前血晶素诱导HO-1表达可逆转上述病理改变(P<0.05)。结论肾内HO-1的诱导表达可明显改善大鼠随后的I/R性肾损伤,作用机制与其增强机体抗氧化能力有关。

To investigate whether heme oxygenase-1 (HO-1) induced attenuates the subsequent renal ischemia-reperfusion (I/R) injury in rats and the possible protective mechanism. 30 male Wistar rats were randomized into three experimental groups of 10 animals each: Sham operation group, I/R group, Hemin group (Hemin 30 mg/kg was administered subcutaneously into rats once a day for two successive days). These rats underwent the renal I/R injury developed by occluding left renal artery for 50 min and then reperfusion for 24 hours. We examined the expression of HO-1 and its activity in renal,serum levels of creatinine (Cr), blood urea nitrogen (BUN), tissue malondialdehyde (MDA) as well as total anti-oxidative capability (TAOC). Compared with I/R group, hemin induced the expression of HO-1 significantly and increased the its activity markedly (P <0.01). Compared with Sham operation group , the serum levels of Cr and BUN and MDA content were significantly higher (P <0.05 respectively) and renal histologic damages showed more severe, but TAOC decreased (P <0.05) in I/R group; the expression of HO-1 before I/R could reverse the changes above. [Conclusion] Our results indicate that the significant expression of HO-1 in the renal can ameliorate subsequent renal I/R injury in rats by its anti-oxidative activity.