氯沙坦治疗对糖尿病肾病患者氧化应激的影响

The effect of Iosartan on treatment oxidative stress in patients with diabetes nephropathy

目的探讨氯沙坦治疗对糖尿病肾病(DN)患者体内氧化应激的影响。方法选择确诊的DN患者64例,在常规降糖治疗的基础上给予氯沙坦100 mg口服,每日1次;另选择健康体检者20例作为健康对照组。全自动生化测定仪测定血糖、血脂,酶联免疫法测定血ox-LDL和尿中单核细胞趋化蛋白-1(MCP-1)含量,分光光度法测定晚期氧化蛋白产物(AOPPs)、超氧化物歧化酶(SOD)、丙二醛(MDA)含量,免疫比色法测定24 h尿蛋白排泄率(UAER)。结果 (1)与健康对照组比较,DN组血清中SOD活性显著降低(P<0.01),MDA、ox-LDL和AOPP含量显著升高(P<0.01)。氯沙坦治疗后,血清中SOD活性显著升高(P<0.01)、MDA、ox-LDL和AOPP含量显著降低(P<0.01)。(2)与健康对照组比较,DN组尿中SOD活性显著下降(P<0.01),而MDA和MCP-1含量显著升高(P<0.01)。氯沙坦治疗后,不仅尿蛋白排泄显著减少(P<0.01),尿中SOD活性明显升高(P<0.01),MDA和MCP-1含量明显降低(P<0.01)。(3)血清中MDA、ox-LDL、AOPP和尿中MCP-1含量与UAER呈显著正相关(r分别为0.88、0.76、0.78、0.81,P均<0.05),而SOD与UAER呈显著负相关(r=-0.79,P<0.05)。结论氯沙坦治疗可显著减少DN患者尿蛋白排泄,可能与其抗氧化抗炎机制有关。

Objective To investigate the effect of losartan on treatment oxidative stress in patients with diabetic nephropathy（DN）.Methods Sixty-four patients with diabetic nephropathy were enrolled to be treated with Losartan（orally,100 mg/d） in addition to routine treatment,and 20 health person were enrolled as control.The level of blood glucose（BG）,triglyceride,total cholesterol,low density lipoprotein（LDL） and 24h urinary protein excretion rate（UAER） were detected by automatically biochemistry radiomete.The concentration of serum or urine ox-LDL and MCP-1 were determined by ELISA.The concentration of serum AOPPs,urine malonaldehyde（MDA） and the activity of serum/urine superoxidedismutase（SOD） were detected by spectrophotography.Results（1） Comparison with health control,the levels of serum MDA,ox-LDL and AOPP were significantly increased（P0.01）,while the activity of serum SOD was decreased markedly in patients with diabetes nephropathy（P0.01）. These changes could be reversed by treatment with losantan for 3 months.（2） The results also showed higher concentrations of urine MDA and MCP-1 as well as lower urine SOD activity in the DN patients compared with control,and the results were reversed by treatment with losantan for 3 months.（3） Relevance analysis demonstrated there were positive correlation between UAER with serum MDA,ox-LDL,AOPP and MCP-1（r=0.88,0.76,0.78,0.81 respectively, P0.05）,but UMER was negatively related with serum activity of SOD（r=-0.79,P0.05）. Conclusion The results indicated that losartan played a role in reducing urinary protein excretion,which the possible mechanism was anti-oxidation and anti-inflammation within kidney.