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目的探讨抗血管紧张素Ⅱ受体拮抗剂缬沙坦不同剂量、不同疗程对糖尿病肾病(DN)抗AT1受体自身抗体阳性患者尿蛋白的影响。方法以合成的AT1受体多肽片段为抗原,应用酶联免疫吸附方法,检测116例DN患者、糖尿病患者60例和正常对照组60例人血清抗AT1受体自身抗体。DN患者均在原胰岛素降糖方案治疗基础上,根据血糖调整降糖药物剂量,自身抗体阴性和阳性组均给予缬沙坦(Valsartan)80mg,每天1次;尼群地平10mg,每天3次;阿斯匹林100mg每天1次,观察缬沙坦对阴性组和阳性组临床降尿蛋白的疗效。随机选择阳性组46例,阴性组39例,给予缬沙坦160mg,每天1次,在服药6个月和12个月后,观察该剂量对尿蛋白的影响。并与服药80mg,每天1次比较。结果DN组抗AT1受体自身抗体阳性率(66.4%,77/116)高于糖尿病组(13.3%,8/60)和对照组(8.3%,5/60),差异有统计学意义(P<0.01)。抗AT1受体自身抗体阳性组缬沙坦(80mg和160mg)治疗12个月尿蛋白改善情况优于治疗6个月;与抗AT1受体自身抗体阴性组比较,具有统计学意义(P<0.01);缬沙坦160mg疗效优于80mg。结论缬沙坦有降低糖尿病肾病抗AT1受体自身抗体阳性患者尿蛋白的作用,靶向治疗具有重要的临床价值。
Objective To investigate the effects of anti-angiotensin Ⅱ receptor antagonist valsartan on urinary protein in patients with diabetic nephropathy (DN) with anti-AT1 receptor autoantibodies at different dosages and different courses. Methods Anti-AT1 receptor autoantibodies were detected in 116 patients with DN, 60 with diabetes mellitus and 60 with normal controls by using synthetic AT1 receptor peptide fragment as antigen. DN patients on the basis of the original insulin hypoglycemic regimen based on blood glucose to adjust the dose of hypoglycemic agents, autoantibodies negative and positive groups were given valsartan (Valsartan 80mg, 1 day; nitrendipine 10mg, 3 times a day; Spirin 100mg 1 times a day to observe the valsartan negative group and the positive group clinical efficacy of proteinuria. Forty-six patients were randomly selected and 39 patients were negative. Valsartan was given 160mg once daily. The effects of this dose on urinary protein were observed after 6 months and 12 months. And medication 80mg, 1 times a day comparison. Results The positive rate of autoantibody against AT1 receptor in DN group (66.4%, 77/116) was significantly higher than that in diabetic group (13.3%, 8/60) and control group (8.3%, 5/60) <0.01). Anti-AT1 receptor autoantibody positive group Valsartan (80mg and 160mg) for 12 months to improve the proteinuria was better than the treatment for 6 months; and anti-AT1 receptor autoantibody negative group compared with statistical significance (P <0.01 ); Valsartan 160mg better than 80mg. Conclusion Valsartan can reduce urinary protein in anti-AT1 receptor autoantibody-positive patients with diabetic nephropathy. Targeted therapy has important clinical value.