双倍剂量氯沙坦对糖尿病肾病患者机体DNA氧化损伤的影响

The effect of double dose Losartan on oxidative DNA damage in diabetic nephropathy

目的探讨不同剂量氯沙坦对2型糖尿病肾病（DN）患者机体DNA氧化损伤的影响。方法选取不吸烟、近期未服用抗氧化药物，且有明显蛋白尿的2型DN患者42例。氯沙坦每天50mg治疗8周，之后每天100mg治疗8周。检测氯沙坦治疗前后24小时尿蛋白、尿肌酐、尿8．羟基脱氧鸟嘌呤（8-OHdG）水平。20例健康志愿者的尿液标本作为对照组。8-OhdG的检测采用毛细管电泳和液相色谱法。结果与对照组比较，糖尿病。肾病患者尿8-OHdG水平明显升高[（22．47±12．18）ng／mgCr，（35．23±17．36）ng／mgCr]，P〈0．01），经氯沙坦50mg／d治疗8周后，8-OHdG水平明显降低（27．25ng／mgCr±15．66ng/mgCr），P〈0．01，经氯沙坦100mg／d治疗8周后，8-OHdG水平进一步降低（21．92ng／mgCr±13．88ng／mgCr），P〈0。01）。结论DN患者机体DNA氧化损伤明显，氯沙坦具有减轻患者DNA氧化损伤的作用，100mg／d比50mg／d的抗氧化应激作用更强，而且副作用无明显增加。氯沙坦的抗氧化应激作用是其对DN患者肾脏保护作用的机制之一。

Objective To observe the antioxidative DNA damage effect of Losartan at doubling dosage in DN patients. Methods 42 cases with type 2 DN patients who did not smoke and did not take antioxidants were recruited. Eligible patients received Losartan 50 mg/day for 8 weeks followed by Losartan 100 mg/day for an additional 8 weeks. 24-hour urine samples of patients were collected to measure urinary protein, creatinine e;icretion and urinary 8-OHdG excretion. Urine samples of 20 volunteers were measured as control. Urinary 8-OHdG were determined by the method of capillary electrophoresis and liquid phase chromatography. Results Compared with the control group,the total 24 h urinary 8-OHdG excretion were significantly increased（35.23 ± 17.36 ng/mgCr vs 22.47 ± 12.18 ng/mgCr,P 〈 0.01 ）. There was an decrease in urinary 8-OHdG levels with losartan 50 rag/day for 8 weeks therapy（27.25 ± 15.66 ng/mgCr,P 〈0.01 ）. Compared with Losartan 50 mg/day,the decrease in urinary 8-OHdG levels with Losartan 100 rag/day is more marked （21.92 ± 13.88 ng/mgCr, P 〈 0.01 ）. Conclusions Oxidative DNA damage is significant in DN patients. Losartan has antioxidative effect in DN patients. Compared with Losartan 50 mg/ day,the antioxidative effect with Losartan 100 rag/day is more marked,and the side effect doesn＇t increase. Losartart＇ s antioxidative effect may be one of the mechanisms of it＇ s beneficial effect on DN protection.