受体拮抗剂靶向治疗对糖尿病肾病患者降低蛋白尿疗效分析

目的观察受体拮抗剂靶向治疗与常规治疗对糖尿病肾脏病减少蛋白尿的临床疗效。方法以合成的β1和AT1受体多肽片段为抗原，应用ELISA技术，检测271例糖尿病肾病患者血清抗8。和AT1受体自身抗体，根据检测结果分为受体自身抗体阳性组171例（阳性组中AT1、β1受体自身抗体均阳性者为靶向治疗组，71例）、受体自身抗体阴性组100例（阴性组中AT1和β1受体自身抗体均阴性者为常规治疗组，57例）和正常对照组40例。治疗组均给予酒石酸美托洛尔（metoprolol tartrate）、缬沙坦、非洛地平、双氯噻嗪、阿司匹林，治疗前后检测尿微量白蛋白和血压，分别观察靶向治疗和常规治疗对降压和减少尿微量白蛋白尿的疗效。结果271例糖尿病肾病患者中受体自身抗体阳性率为63．1％（171／27I），阴性率为36．9％（100／271），阳性率明显高阴性率，同样其阳性率明显高于正常对照组的12．5％（5／40），差异均有统计学意义（P〈O．05）.靶向治疗组降压及减少蛋白尿疗效明显优于常规治疗组（P〈0．01o结论糖尿病肾脏病患者通过抗β1和AT1受体自身抗体检测，有针对性的酒石酸美托洛尔和缬沙坦受体拮抗剂靶向治疗，可提高降压及减少蛋白尿疗效且较安全。

Clinical Efficacy of Targeted Therapy with Receptor Antagonist on Albuminuria in Patients with Diabetic Nephropathy

Objective To investigate the efficacy of targeted therapy of receptor antagonist on albuminuria in patients with diabetic kidney disease. Methods The epitopes of the second extracellular loop of β1 receptor （197-222） and AT1 receptor （165-191） was synthesized and used respectively to screen out sera autoantibodies from patients with diabetic nephropathy （n= 271） and the control group （n=40） by ELISA. According to the results, the patients with diabetic nephropathy were divided into two groups： the autoantibody positive group （n=171）, 71 of them who had both positive of autoantibodies against β1 receptor and AT1 receptor were selected as targeted therapy group and taken target therapy based on conventional treatment; and the autoantibody negative group （n=lO0）, 57 of them who had both negative of autoantibodies against β1 receptor and AT1 receptor were selected as the conventional therapy group. The patients in two group were given the following medication respectively： Metoprolol Tartrate 25-50 mg, po, tid; Valsartan80-160 mg, po, qd ; Aspilin 100 mg, po, qd ; felodipine 5 rag, po, qd ; Hydrochlorothiazide 12.5 mg, po, qd. The hypertension of all subjects was measured before and after 1-4 weeks treatment. The 24-hour urinary protein （UAER） was measured before and after 6-month treatment. Results In patients with diabetic nephropathy, the total positive rate of the autoantibody againstβ1 receptor and AT1receptor was 63.1% （171/271） and the positive rate of antibodies both against β1 receptor and AT1receptor was 41.5%（71/171）, all higher than that in the control group （12.5%, 5/40）（P〈0.01）. The decrease of blood pressure and urine protein were significantly lower than those in the conventional treatment group （P〈0.01）. Conclusion The findings suggest that these autoantibodies against β1 and AT1-receptor may play important roles in the pathogenesis of diabetic nephropathy. Metoprolol Tartrate and Valsartan was shown to be effective and safe in the treatment of diabetic kidney disease.