美托洛尔联合贝那普利对β_1、AT_1受体自身抗体阳性的糖尿病肾病患者尿白蛋白的影响

Effects of combined therapy with metoprolol and benazepril on urinary albumin excretion in diabetic nephropathy patients with positive autoantibodies against β_1-adrenergic and AT_1 receptor

目的探讨美托洛尔联合贝那普利对β_1肾上腺素受体(β_1受体)和血管紧张素Ⅱ受体1型(AT_1)受体自身抗体阳性的糖尿病肾病(DN)患者尿白蛋白的影响。方法以合成的β_1和AT_1受体多肽片段为抗原,应用ELISA技术,检测471例DN患者(DN组)、107例2型糖尿病患者(T2DM组)、47名正常对照者(NC组)的β_1和AT_1受体自身抗体。DN组中β_1和AT_1受体自身抗体均阳性的为Ab+组,其余为Ab一组。Ab+组和Ab组均给予美托洛尔25～50 mg,日3次;贝那普利10 mg,日1次;尼群地平10～20 mg,日3次;阿司匹林100 mg,日 1次,口服。用ELISA技术测定尿白蛋白排泄率。结果 (1)DN组抗β_1和AT_1受体自身抗体阳性率分别为54.6%(257/471)和51.2%(241/471),两抗体均阳性为50.3%(237/471),均明显高于T2DM组的15.9%(17/107)、10.2%(11/107)和8.4%(9/107),以及NC组的10.6%(5/47)、8.5%(4/47)和6.4%(3/47)(P<0.01)。(2)DN组中Ab+组尿白蛋白降低明显优于Ab组(P<0.01)。结论美托洛尔联合贝那普利治疗β_1和AT_1受体自身抗体阳性的DN患者,其降低白蛋白尿的疗效明显提高,靶向治疗具有重要的临床价值。

Objective To observe effect of combined therapy with metoprolol and benazepril on urinary albumin excretion rate （UAER） in diabetic nephropathy （DN） patients with positive autoantibodies against β1-adrenergic and AT1 receptor. Methods The study subjects included DiN （n=471）, T2DM （n--107） and normal control （n=47）. Autoantibobies against β1-adrenergic and AT1 receptor, as well as UAER were determined by ELISA. Both positive and negative autoantibodies groups were given metoprolol 25-50 mg three times daily, benazepril 10 mg daily, nitrendipine 10-20 mg three times daily, aspirine 100 mg daily. Results The DN group showed higher positive rates of β1R-Ab, ATtR-Ab and β1R-Ab＋AT1R-Ab （54. 6%, 51. 2% and 50. 3%, respectively） than did T2DM （15. 9%, 10. 2%, 8.4%, respeebively） and did normal control （10. 6%, 8. 5% and 6. 4%, respectively） （P〈0. 01）. The UAER decrement was higher in Ab （＋） group than in Ab （-） group. Conclusion The combined therapy of DN patients with β1 R- Ab （ ＋ ） and AT1 R- Ab （＋） with metoprolol and benazepril could obviously reduce UAER. Immunologieally targeted therapy has a very important clinical value.