2型糖尿病并难治性高血压抗β1肾上腺素能和M2胆碱能受体自身抗体与蛋白尿的关系

The relation between positive rate of autoantibodies against β1 and M2-adrenergic receptors and urinary albumin excretion rate in the type 2 diabetes mellitus with refractory hypertension

目的探讨糖尿病并难治性高血压患者β1和M2受体自身抗体与蛋白尿的关系。方法以合成的β1和M2受体多肽片段为抗原，应用酶联免疫吸附测定（ELISA）技术，检测136例糖尿病并难治性高血压患者[A组，A组分为蛋白尿组（尿蛋白排泄率≥20μg,／min，91例）和正常蛋白尿组（UAER〈20μg／min，45例），蛋白尿组根据UAER水平分为蛋白尿1组（UAER≥200μg,／min）和蛋白尿2组（UAER20～199μg,／min）]；111例糖尿病并高血压患者（B组）；60例高血压无肾损患者（C组）及40例正常人（D组）。血清中抗G-蛋白偶联型β1和M2受体自身抗体，尿蛋白排泄率用ELISA技术检测。结果（1）A组抗β1和M2受体抗体阳性率为44．9％（61／136）和37．5％（51／136），明显高于B组的27．9％（31／111）和24．3（27／111）明显高于C组的11．7％（7／60）和15．0％（9／60）及D组8．3％（5／40）和7．5％（3／40），组间比较差异有统计学意义（P〈0．01）。（2）A组中蛋白尿组抗β1和M2受体抗体阳性率分别为60．4％（55／91）和50．5％（46／91）明显高于A组中正常蛋白尿组13．3％（6／45）和11．1％（5／45），组间比较具有统计学意义（P〈0．01）。（3）蛋白尿1组抗β1和M2受体自身抗体阳性率为87．1％（27／31）和67．7％（21／31），明显高于蛋白尿2组的46．7％（28／60）和41．7％（25／60）及正常蛋白尿组的13．3％（6／45）和11．1％（5／45），组间比较差异有统计学意义（P〈0．01）。结论肾损害越严重，尿蛋白水平越高，抗β1和M2受体自身抗体阳性率也越高。提示自身免疫机制参与可能是引起糖尿病并难治性高血压肾损害的重要因素之一。

Objective To explore the relation between the positive rates of autoantibodies against β1 adrenergic receptor（ β1-receptor） and （M2 -receptor）with urinary albumin excretion rate （UAER）in type 2 diabetes patients with refractory hypertension. Methods Autoantibodies against β1and M2-receptor as well as autoantibodies were determined in type 2 diabetes patients with （n = 136） or without （n = 111 ） refractory hypertension, hypertensive patients without renal failure （ n = 60 ） and healthy control subjects （n =40, control） by ELISA. Results The positive rates of the autoantibodies against β1-receptors （44. 9% ） and M2-receptor （37. 5% ） in patients with type 2 diabetes with refractory hypertension were significantly higher than those in patients with type 2 diabetes without refractory hypertension （27. 9% and 24. 3%, respectively, all P 〈 0. 05 ）, in patients with hypertension without renal failure （11.7% and 15.0%, all P 〈 0. 01 ） and in healthy controls （ 8. 3% and 7.5%, all P 〈 0. 01 ）. In type 2 diabetes patients with refractory hypertension and renal failure （ UAER ≥ 200 μg/min ）, the positive rates of the autoantibodies against β1-receptor （87.1%, 27/31 ）and against M2-receptor （67.7%, 21/31 ）were significantly higher than those in type 2 diabetes patients with refractory hypertension but without renal failure （UAER 20-199 μg/min, 46.7%, 28/60 and 41.7% ,25/60, respectively, all P 〈0. 05） . Conclusion The serum β1-and M2-receptor autoantibodies are positively associated with the UAER level and suggest that these autoantibodies against β1 and M2-receptor may play important roles in the pathogenesis of the type 2 diabetes with refractory hypertension.