风湿性心脏病患者血清抗β_1肾上腺素受体自身抗体的生物学效应  

Biological effects of autoantibody against β_(1)-adrenoceptor in patients with rheumatic valvular heart diseases

作　　者：贺忠梅[1] 李美霞[1] 王晓樑[1] 王晋萍[2] 汤嘉宁[3] 魏书庆[3] 刘慧荣[1] 

机构地区：[1]山西医科大学生理学教研室,山西太原030001 [2]山西医科大学山西省心血管病研究所,山西太原030001 [3]山西医科大学附属太钢总院,山西太原030001

出　　处：《心脏杂志》2006年第2期194-197,共4页Chinese Heart Journal

基　　金：山西省自然科学基金项目资助(No.20021103);山西省教育厅普通教育基金项目资助(No.200476)

摘　　要：目的探讨风心病患者血清中抗β1肾上腺素能受体(β1AR)自身抗体的生物学效应。方法①应用SA-ELISA方法,检测风心病患者(60例),正常人(97例),以及心衰大鼠(33只)和对照大鼠(20只)血清标本中的抗β1AR自身抗体;②亲和层析法纯化风心病患者、心衰大鼠抗体阳性血清中的IgGs;③观察抗β1AR自身抗体IgGs对乳鼠心肌细胞搏动频率的影响;④测定抗β1AR自身抗体IgGs对成年大鼠心肌细胞腺苷酸环化酶活性的影响。结果风心病患者血清中抗β1AR自身抗体的阳性率和抗体滴度分别为43%和1∶(98.3±1.6),均显著高于正常人的4%和1∶(14.6±2.7),P<0.01,类似的结果见于心衰大鼠[85%,1∶(67.3±2.4)]与对照大鼠[5%,1∶(17.3±2.1)](P<0.01)之间;纯化的风心病患者、心衰大鼠抗β1AR抗体IgGs均可增加乳鼠心肌细胞的搏动频率,且在6 h内不脱敏;还可增强成年大鼠心肌细胞的腺苷酸环化酶活性,使cAMP产生量增加。结论风心病患者血清中的抗β1AR自身抗体具有激动剂样刺激效应,即具有正性变时效应(不易脱敏)、可增强腺苷酸环化酶活性。提示抗β1AR自身抗体可能是风心病患者神经体液调节功能紊乱的原因之一。AIM To determine the biological effects of autoantibody against β1-adrenoceptor in patients with rheumatic valvular heart diseases （RVHD）. METHEDS ①Synthetic peptides corresponding to amino acids of the second extracellular loops of the β1-adrenoceptor used as the antigen to screen the sera from RVHD patients （n = 60） , normal control （NC, n = 97） , rats with heart failure （n = 33） and control rats （ n = 20） by using SA-ELISA. ② IgGs from the positive sera of the patients with RVHD and rats with heart failure were prepared by using a MabTrap Kit （Amersham） following the manufacturer＇ s instructions. ③ The effects of IgGs from the positive sera on the beating rate of cultured neonatal rat cardiomyocytes were observed. ④ By using radioimmunoassay technique, the activity of adenylyl cyclase （AC） in adult rat cardiomyocytes was observed. RESULTS The positive rate and titer of anti-β1-adrenoceptor autoantibody from the patients with RVHD were obviously higher than those from normal control [43%, 1 ： （98.3 ± 1.6） ] vs [ 4%, 1 ： （ 14.6 ± 2.7 ） ], （ P 〈 0.01 ） and similar result was found in rats with heart failure and control rats [ 85%, 1 ： （67.3 ± 2.4） ] vs [ 5%, 1 ： （ 17.3 ± 2.1 ） ], （ P 〈 0.01 ）. The IgGs from patients with RVHD and rats with heart failure not only increased the beating rate of cultured neonatal rat cardiomyocytes and non-desensitization in 6 hours, but also enhanced the activity of AC in adult rat cardiomyocytes and increased the cyclic adenosine monophosphate （cAMP） content. CONCLUSION Like β1- adrenoeeptor agonists, the autoantibody against β1-adrenoeeptor in patients with RVHD induces positive ehronotropie effects, indicating that the autoantibody against β1-adrenoeeptor functions as an agonist and participates in the pathophysiologieal mechanisms of RVHD.

关 键 词：风湿性心脏病 Β1肾上腺素能受体 自身抗体 生物效应 

分 类 号：R541.2[医药卫生—心血管疾病]