糖尿病肾病抗AT_1受体自身抗体阳性患者靶向治疗对尿蛋白的控制

Clinical Evaluation of Valsartan in Treatment of the Positive Autoantibodies against AT_1 Receptor in Patients with Diabetic Nephropathy

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 observe the therapy effect of different dose and time of valsartan, angiotensin Ⅱ 1 receptor antagonist （AT1Ra）, on urine protein in diabetic nephropathy patients with positive AT1R autoantibody. Methods The epitopes of AT1R was synthesized and used respectively to screen serum autoantibody from 116 hypertensive patients with diabetic nephropathy （DN）, 60 patients with diabetes mellitus （DM） and 60 healthy blood donors as control, by ELISA. In DN group, patients were divided into two subgroups （PA group： 77 patients with positive autoantibody against AT1R as the treatment group; NA group： 39 patients with negative autoantibody against AT1R as the control） and were given the following drugs treatment respectively： Valsartan 160 mg po, qd, Aspilin 100 mg po, bd, Nitrundiping 10 mg po, tid. After 6 and 12 month period therapy, the 24-hour urinary protein was improved significantly in PA group than in NA group, in 12 month treatment than in 6 month treatment, and in 160 mg treatment than in 80 mg treatment, respectively. Results In patients diabetic nephropathy was 66.4%, they were higher than those of diabetes mellirus and of healthy donors （13.3% and 8.3% respectively）, Valsartan reduced proteinufia significantly （P〈0.01） in diabetic nephropathy patients with the positive rates group of the autoantiboclies against AT1 receptor. Conclusion Valsartan significantly protect renal function in hypertensive patients of diabetic nephropathy with the positive autoantibody against AT1 receptor.