苦参素降低大鼠肾脏缺血-再灌注损伤

Oxymatrine attenuates ischemia/reperfusion injury in rat kidneys

目的观察苦参素的抗大鼠肾缺血再灌注损伤的作用并从抗氧化方面探讨其机制。方法用双肾肾蒂夹闭45 min建立IRI模型,将SD大鼠随机分为假手术组(sham);缺血再灌注组(I/R);苦参素治疗组(oxymatrine+I/R)。苦参素治疗组又分为高、中和低3个剂量组,在缺血再灌注前,连续7 d经腹腔注射。用自动生化仪测定血清肌酐(Scr)和尿素氮(BUN)水平,观察苦参素对肾缺血再灌注的保护作用及确定最优剂量;以最优剂量干预用分光分析法测定肾组织丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、超氧化物歧化酶(SOD)水平。结果不同剂量组均能明显减轻肾脏IRI的病理形态学改变,改善肾功能。与I/R组相比,再灌注72 h后,MDA水平,血清肌酐(Scr)和尿素氮(BUN)水平明显降低(P<0.05);苦参素治疗组的CAT、T-SOD、GSH-Px活性改善明显(P<0.05)。苦参素无体外抗氧化作用。结论苦参素对大鼠肾缺血再灌注损伤具有保护作用,作用机制可能与调控机体的抗氧化系统有关。

Objective Renal ischemia followed by reperfusion leads to acute renal failure, which is a complex pathophysiologic process involving hypoxia and free radical （FR） damage. We aimed to investigate the effect of oxymatrine on kidney ischemia/reperfusion （I/R） injury and the antioxidant effects of oxymatrine in rats. Methods SD rats were randomly divided into 5 groups （ I/R group, sham operation group and oxymatrine treatment groups）. Rats in the I/R group were subjected to bilateral renal ischemia for 45 min and followed by reperfusion. Rats in the oxymatrine treatment groups received oxymatrine intraperitoneally （ i. p. ） at 3 different doses before I/R for 7 days. In some experiments, rats were killed and kidney function, tissue catalase （CAT）, malondialdehyde （MDA） levels, superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） activities were determined. Results Oxymatrine significantly prevented I/R-induced kidney injury as indicated by decreased serum creatinine（Scr） andblood urea nitrogen （BUN） levels compared to I/R group （P 〈0. 05）. Reduction of tissue CAT, SOD and GSFI- Px activities after I/R were significantly improved by oxymatrine （P 〈 0. 05 ）. Treatment with oxymatrine also resul- ted in significant reduction in tissue MDA that was increased by renal I/R injury （ P 〈 0.05 ）. Conclusions Based on our results, it could therefore be concluded that oxymatrine protects the kidneys against I/R injury at least partly via its antioxidant effects.