抗β_1肾上腺素能受体自身抗体在糖尿病心肌病并高血压发病中的致病机制及临床干预

Metoprolol Tartrate for Diabetic Myocardial Disease with Positive Autoantibodies against β_1 Receptor

目的探讨抗G蛋白偶联β1肾上腺素能受体自身抗体致病作用及临床干预。方法以合成的β1受体多肽片段为抗原,应用酶联免疫吸附测定（ELISA）技术,检测171例人血清中抗G蛋白偶联β1受体自身抗体,其中糖尿病心肌病患者71例,2型糖尿病60例及正常对照组40例。对糖尿病心肌病受体自身抗体阳性的为治疗组,阴性的为对照组,两组均在常规强心利尿基础上给予缬沙坦80mg,po,qd;硝酸异山梨醇酯（isosorbide dinitrate）10mg,po,tid;酒石酸美托洛尔（metororolol tartrate）25mg po,bid;双氯噻嗪12.5mgpo,qd;阿斯匹林100mg po,qd,分别观察阳性组和阴性组对心功能的影响,6～12个月采用超声心动图进行对比观察。结果糖尿病心肌病组抗β1受体阳性率为57.7%（41/71）,明显高于糖尿病无心肌病组18.3%（11/60）及正常对照组17.5%（7/40）,比较具有统计学意义（P〈0.01）。阳性组反映左室形态、收缩、舒张功能的指标明显改善（P〈0.05）,阳性组优于阴性组,阳性组总有效率为82.9%,阴性组56.7%。结论免疫学机制可能参与糖尿病心肌病病理生理过程;酒石酸美托洛尔可明显改善心功能。

Objective To explore the role of the autoantibodies against β1-adrenergic receptor in the development of diabetic myocardial disease （DC） and to observe the effect of β1 receptor antagonist metoprolol tartrate on DC.Methods The epitopes of the second extracellular loop of β1 receptor （197-222） were synthesized to screen sera autoantibodies from the patients with DC （n=71）, type 2 diabetes mellitus （DM, n=60）, and healthy blood donors （n=40） by ELISA. The patients with DC were divided into two groups： positive autoantibodies against β1 receptor （experimental group, n=41）） and negative autoantibodies against β1 receptor （DC control group, n=30） and they were given the following drugs as regimen： isosorbide dinitrate 10 mg, po, tid, metoprolol tartrate 25 mg po, bid; hydrochlorothiazide 12.5 mg po, qd, aspirin 100 po, qd, valsartan 80 mg po, qd. During 24-48 weeks after the start of the treatment, the changes of cardiac function in the two groups were observed. Echocardiography was performed to compare some cardiac parameters before and after the treatment in double blindness.Results The positive rate of autoantibodies against β1 receptor in DC patients was 57.7% （41/71）, significantly higher than that in DM patients （18.3%, 11/60） and in healthy blood donors （17.5%, 7/40） （P〈0.01）. The indexes of left ventricular systolic function （LVESV, EDV, FS, SV, CO and EF） and of left ventricular diastolic function （VmaxE, VmaxA, E/A, VTIE, E-VTI/A-VTI） had been significantly improved in the experimental group, compared to those in DC control group （P〈0.05, P〈0.01）. The total effective rate of cardiac function improvement was 82.9% in the experimental group, higher than that in DC control group （56.7%）.Conclusion Autoantibodies against β1 receptor were higher in DC patients, so that they may play important roles in the pathogenesis of diabetic myocardial disease. Metoprolol tartrate can improve left ventricular diastolic and systolic function.