低分子右旋糖酐铁和蔗糖铁对慢性肾衰竭大鼠氧化应激的影响

Effects of low molecular weight iron dextran and iron sucrose on oxidative stress in chronic renal failure of subtotal nephrectomized rats

目的 评价小剂量反复多次低分子右旋糖酐铁和蔗糖铁静脉用药后对慢性肾衰竭大鼠氧化应激的影响.方法 以5/6肾大部切除术建立慢性肾衰竭大鼠模型.右肾切除术后第4周,将实验大鼠分为4组：低分子右旋糖酐铁（糖酐铁）组、蔗糖铁组、对照组、假手术组.观察6周,检测各组大鼠体内氧化应激、铁代谢等指标.结果 糖酐铁组和蔗糖铁组大鼠血红蛋白明显高于对照组（P＜0.05）,而两铁剂组间差异无统计学意义.对照组大鼠的血清铁、血清铁蛋白、转铁蛋白饱和度显著低于假手术组（P＜0.05）;两铁剂组大鼠上述指标均显著高于对照组（P＜0.05）,而两铁剂组间差异无统计学意义.糖酐铁组和蔗糖铁组血浆晚期氧化蛋白产物（AOPP）显著高于对照组[（127.84±21.19）μmol/L、（134.21±29.38）μmol/L比（81.83±19.93）μmol/L,P＜0.05],而两铁剂组间差异无统计学意义.两铁剂组大鼠血浆丙二醛（MDA）高于对照组,而蔗糖铁组高于糖酐铁组[（6.06±0.73）nmol/L 比（4.99±0.80）nmol/L,P＜0.05].糖酐铁组、蔗糖铁组和对照组大鼠血清超氧化物歧化酶（SOD）和总抗氧化能力（TAOC）差异无统计学意义.模型组大鼠血浆谷胱甘肽过氧化物酶（GSH-Px）水平显著低于假手术组（P＜0.05）,而蔗糖铁组显著低于糖酐铁组和对照组[（2123.1l±74.78）nmol·ml-1·min-1比（2352.84±163.90）nmol·ml-1·min-1、（2310.23±125.99）nmol·ml-1·min-1,P＜0.05].结论 静脉补铁可部分纠正5/6肾大部切除肾衰竭大鼠的贫血,改善铁代谢指标.反复静脉小剂量补铁对慢性肾衰竭大鼠氧化应激状态有不良影响,而低分子右旋糖酐铁的不良影响低于蔗糖铁.

Objective To investigate the effects of repeated low dose intravenous infusion of low molecular weight iron dextran and iron sucrose on oxidative stress in chronic renal failure （CRF） rats. Methods CRF model was established by 5/6 subtotal nephrectomy （5/6 Nx）. Four weeks after removing the right kidney, successful rats were randomly divided into low molecular weight iron dextran group, sucrose iron group and CRF control group. The sham group was established simultaneously. The dose of iron administrated in each rat was similar in iron dextran group and sucrose iron group. There were 6 rats in each group. Animals were observed for 6weeks, then the blood, urine and renal tissue samples were collected, and indexes of renal function,anemia, iron status and oxidative stress were investigated. Results The hemoglobulin （Hb） level in iron groups was significantly higher as compared to control group （P〈0.05） but was not significantly different between two iron groups. The levels of serum iron, ferritin and saturation rate of transferring （TS） were obviously lower in control group as compared to sham group （P〈0.05）.Levels of above 3 indexes were significantly higher in two iron groups as compared to control group （P〈0.05）, but were not significantly different between two iron groups. Concentration of plasma advanced oxidation protein products （AOPP） was obviously higher in two iron groups than that in control group [（127.84±21.19） μmol/L, （134.21±29.38） μmol/L vs （81.83±19.93） μmol/L, P〈0.05]. Plasma malonaldehyde （MDA） was significantly higher in iron sucrose group than that in iron dextran group [（6.06±0.73） nmol/L vs （4.99i0.80） nmol/L, P〈0.05]. Serum levels of superoxide dismutase （SOD） and total anti-oxidant capacity （TAOC） had no significant differences among three CRF groups. Concentration of plasma glutathione peroxidase （GSH-Px） was significantly decreased in three CRF groups as compared to sham group （P〈0.05）, while plasma GSH-Px was significantly lower in sucrose iron group than that in iron dextran group and control group [（2123.11±74.78）nmol ·ml-1 ·min-1 vs （2352.84±163.90） nmol· ml-1 ·min-1, （2310.23±125.99） nmol ·ml-1 ·min-1, P〈0.05]. Conclusions Injection of intravenous iron can partially improve the anemia and the iron status indexes in 5/6 Nx CRF rats. Repeated low dose intravenous infusion of iron dextran and iron sucrose can aggravate the oxidative stress state in CRF rats, and the iron sucrose is worst.