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目的探讨血管紧张素受体阻断剂洛沙坦随剂量增加对糖尿病肾病(DN)患者氧化应激的影响。方法收集30例不吸烟、近期未服用抗氧化药物,并且存在明显蛋白尿的2型 DN患者,经4～6周洗脱后,洛沙坦每天50 mg治疗8周,之后每天100 mg治疗8周。治疗期间控制血压、血糖不变。每两周检测患者24 h尿蛋白、尿肌酐、尿8-羟基脱氧鸟嘌呤(8-OHdG)、新鲜尿超氧化物歧化酶(SOD)、总抗氧化能力(TAOC)、丙二醛(MDA),以及血清SOD、TAOC、 MDA。比较SOD、TAOC、MDA及8-OHdG的改变。结果患者治疗前24 h尿8-OHdG浓度、血清MDA浓度明显高于正常值,血和尿SOD浓度明显低于正常值。洛沙坦50 mg／d治疗后上述指标有好转;经加大到100 mg／d后,24 h尿8-OHdG浓度、血和尿MDA浓度进一步下降(P< 0．01),血和尿SOD浓度也进一步明显上升(P<0．01),同时24 h尿蛋白减少,但差异无统计学意义。观察期间无严重不良反应发生。结论 DN患者机体氧化应激损伤活跃。洛沙坦对DN患者具有抗氧化应激作用,洛沙坦100 mg／d比50 mg／d的抗氧化应激作用更强,而且不良反应无明显增加。
Objective To investigate the effects of losartan, an angiotensin receptor blocker inhibitor, on oxidative stress in patients with diabetic nephropathy (DN). Methods Thirty patients with type 2 DN who did not take anti-smoking drugs, who had not taken anti-oxidant drugs recently and had obvious proteinuria were enrolled. After 4 to 6 weeks of elution, losartan was treated with 50 mg daily for 8 weeks and 100 mg daily after 8 week. Control of blood pressure during treatment, blood glucose unchanged. Urinary protein, urinary creatinine, 8-OHdG, fresh superoxide dismutase (SOD), total antioxidant capacity (TAOC), malondialdehyde (MDA) ), As well as serum SOD, TAOC, MDA. The changes of SOD, TAOC, MDA and 8-OHdG were compared. Results The urinary 8-OHdG concentration and MDA level in serum of patients 24 hours before treatment were significantly higher than those of normal values, and the concentrations of SOD in serum and urine were significantly lower than those in normal subjects. Losartan 50 mg / d after treatment, the above indicators have improved; increased to 100 mg / d, 24 h urine 8-OHdG concentration, blood and urine MDA levels decreased further (P <0.01), blood and urine SOD concentration also further increased significantly (P <0.01), while 24 h proteinuria decreased, but the difference was not statistically significant. No severe adverse reactions occurred during the observation period. Conclusion DN patients have active oxidative stress injury. Losartan has anti-oxidative stress effects on DN patients. Losartan 100 mg / d is more effective than anti-oxidant stress at 50 mg / d, and no adverse reaction is observed.