慢性肾脏病患者低分子肝素抗氧化作用的研究

The effect of low molecular weight heparin as an antioxidant in chronic kidney disease

目的阐明在慢性肾脏病(chronic kidney disease,CKD)时低分子肝素是否具有抗氧化作用,为临床治疗提供理论依据。方法选取CKD3～5期住院患者40例,随机分为低分子肝素(low molecular weight heparin,LMWH)组(速碧林0.4ml/d皮下注射,连续10d)及还原型谷胱甘肽(reduced glutathione,GSH)组(泰特1.8g/d加入0.9%NaCl溶液静脉滴注,连续10d)。测定2组用药前后血浆氧化应激指标谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-PX)、丙二醛(malondialdehyde,MDA)、晚期氧化蛋白产物(advanced oxidation protein products,AOPP),并观察药物不良反应。结果 LMWH及GSH治疗后血浆AOPP水平均显著降低(P<0.05),GSH组AOPP降低值显著高于LMWH组,分别为(4.89±0.66)ìmol/L和(2.86±0.82)ìmol/L,差异有统计学意义(P<0.05);LMWH及GSH治疗后GSH-PX活力均显著升高(P<0.05),LMWH组和GSH组GSH-PX升高值分别为(3.55±1.01)×104U/L和(4.77±1.78)×104U/L,差异无统计学意义(P>0.05);LMWH治疗前后MDA分别为(5.54±1.66)nmol/ml和(5.42±1.40)nmol/ml,差异无统计学意义(P>0.05),GSH治疗后MDA活力比治疗前显著降低,分别为(5.09±1.44)nmol/ml和(4.61±1.30)nmol/ml,差异有统计学意义(P<0.05)。两组药物治疗期间均未见明显不良事件。结论 LMWH可以改善CKD患者氧化应激状态,短期应用未见明显不良反应。与GSH相比,LMWH的抗氧化作用稍弱。

Objective To identify the anti-oxidative effect of low molecular weight heparin （LMWH） in chronic kidney disease （CKD）. Method Forty CKD patients at stage 3-5 were randomly divided into two groups, glutathione （GSH） group （0.9% NaCl 250ml ＋ Glutathione 1.8g/d, intravenous injection for 10 days） and LMWH group （Fraxiparine 0.4ml/d, subcutaneous injection for 10 days）. Plasma malondialdehyde （MDA）, advanced oxidation protein product （AOPP） and glutathione peroxidase activity （GSH-PX） were measured at the beginning and the end of glutathione or LMWH administration. Results Plasma AOPP decreased and plasma GSH-PX increased significantly after the treatment in both LMWH and GSH groups （P0.05）. The decrease of plasma AOPP was more significant in GSH group than in LMWH group （2.86±0.82 vs. 4.89±0.66μmol/l, P0.05）. After the treatment, plasma MDA did not change significantly in LMWH group, but decreased （5.09±1.44 vs. 4.61±1.30nmol/ml, P0.05） in GSH group. There were no apparent side effects in both groups. Conclusion LMWH ameliorates oxidative stress state without apparent side effects. The anti-oxidative effect of LMWH is slightly lower than that of GSH.