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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 investigate the relationship between metoprolol and benazepril in patients with diabetic nephropathy (DN) who have autoantibodies to β_1 adrenoceptor (β_1 receptor) and angiotensin Ⅱ receptor type 1 (AT_1) autoantibodies influences. Methods Using the synthetic β 1 and AT 1 receptor peptide fragments as antigen, the levels of β 1 in 471 patients with DN (DN group), 107 patients with type 2 diabetes (T2DM group) and 47 normal controls (NC group) And AT_1 receptor autoantibodies. In DN group, the autoantibodies of β 1 and AT 1 receptor were positive in Ab + group and the rest in Ab group. Metoprolol was administered in the Ab + and Ab groups for 25-50 mg three times daily, benazepril 10 mg once daily, and nitrendipine 10-20 mg three times daily, aspirin 100 mg once daily ,oral. Urinary albumin excretion rate was measured by ELISA. Results (1) The positive rates of anti-β_1 and AT_1 receptor autoantibodies in DN group were 54.6% (257/471) and 51.2% (241/471), respectively. The positive rates of both antibodies were 50.3% (237/471) 15.9% (17/107), 10.2% (11/107) and 8.4% (9/107) in the T2DM group and 10.6% (5/47), 8.5% (4/47) and 6.4% in the NC group (3/47) (P <0.01). (2) The levels of urinary albumin in Ab + group in DN group were significantly lower than those in Ab group (P <0.01). Conclusion The combination of metoprolol and benazepril in the treatment of DN patients with autoantibodies to β_1 and AT_1 receptors significantly improves the efficacy of reducing albuminuria. Targeted therapy has important clinical value.