心力衰竭患者抗β_3肾上腺素能受体自身抗体的分布及特性  

Distribution and property of anti-β_3-adrenoceptor autoantibody in patients with heart failure

作　　者：李美霞[1] 王晓樑[1] 汤嘉宁[2] 刘晓军[3] 田珏[1] 闫莉[1] 刘慧荣[1] 

机构地区：[1]山西医科大学生理教研室,太原030001 [2]太原钢铁集团公司总医院 [3]中国协和医科大学基础研究所

出　　处：《中华心血管病杂志》2005年第12期1114-1118,共5页Chinese Journal of Cardiology

基　　金：山西省自然科学基金项目(20021103);山西省资助回国留学人员科研项目(200526)

摘　　要：目的探讨心力衰竭(心衰)患者血清中的抗β3肾上腺素能受体(β3-AR)自身抗体的生物学效应,为临床治疗心衰提供新的思路和线索。方法(1)以人β3-AR细胞外第二环的合成肽段作为抗原,采用ELISA筛选正常人和心衰患者血清中抗β3-AR自身抗体。(2)提纯该抗体阳性的患者血清中的IgG。(3)设立各组对照观察该抗体对成年大鼠心肌细胞收缩效应的影响。(4)设立各组对照观察该抗体对乳鼠心肌细胞跳动频率的影响。结果(1)正常人抗β3-AR自身抗体的阳性率为11.0%,平均滴度为1∶14.59±1.61;心衰患者抗β3-AR自身抗体的阳性率为26.7%,平均滴度为1∶43.27±2.71;与正常人相比,P<0.05。(2)与空白对照组相比,该抗体可降低成年大鼠心肌细胞收缩幅度/初长度(3.84%±0.33%)、收缩速率(-0.47μm/s±0.07μm/s)和舒张速率(0.17μm/s±0.02μm/s),P<0.05。该作用不能被纳多洛尔(nadolol,β1-AR和β2-AR受体拮抗剂)阻断,但可被布拉洛尔(bupranolol,非特异性β受体拮抗剂)或β3抗原阻断。(3)与空白对照组(94.3次/min±10.7次/min)相比,该抗体可降低乳鼠心肌细胞跳动频率(47.1次/min±8.11次/min),P<0.05。同样该作用不能被纳多洛尔阻断,但可被布拉洛尔或β3抗原阻断。此外,该抗体的负性变时效应在观察时间内(6h)无衰减。结论心衰患者血清中含有较高滴度的抗β3-AR自身抗体并具有负性变力和变时效应,提示该抗体可能参与心衰的病理生理机制。Objective To investigate the biological effects of anti-63 adrenoceptor （63-AR） autoantibody in the serum of patients with heart failure, which may contribute to a new therapeutic clue for heart failure. Methods The synthetic peptide of the second extracellular loop of the 63-AR was used as the antigen to screen sera of patients with heart failure and of healthy controls by using enzyme-linked immunosorbent assay. IgG in the patients group of positive autoantibody sera was prepared by using a MabTrap Kit （Amersham） following the manufacturer＇s instructions. The effects of IgG per each group both on contractile response of adult isolated cardiomyocytes and on beating frequency of cultured neonatal rat eardiomyocytes were observed. Results The positive rate of anti-β3-AR autoantibody was 26.7% （ mean antibody titer： 1：43.27 ±2.71 ） or 11.0% （ mean antibody titer： 1：14.59 ± 1.61 ） in patients or healthy subjects, respectively P 〈 0.05. Compared with the control group, the autoantibody against 63-AR from the patients group decreased cell shortening amplitude/cell shortening 3. 84% ± 0. 33%, the velocity of shortening -0. 47 μm/s ±0.07 μm/s and relengthening 0. 17 μm/s ±0.02 μm/s in adult isolated cardiac myocytes, respectively. The autoantibody in the patients group decreased the beating rate in cultured neonatal rat cardiac myocytes by 47. 1 beats/min ± 8. 11 beats/min, which could have a 6-hour continuance. This decreasing was not modified by Nadolol （ 61-AR and 62-AR antagonist） in pretreating myocytes, but was nearly prevented by Bupranolol （nonselective 6-AR antagonist） or 63-AR specific antigen. Conclusion It seems reasonable to state that a high titer of the autoantibody against 63-AR in the serum in patients with heart failure, which could have a negative inotropic and chronotropic effect, may be a part of pathophysiological mechanisms of heart failure.

关 键 词：心力衰竭 充血性 受体 肾上腺素能β6 自身抗体 Β3肾上腺素能受体 心力衰竭患者 成年大鼠心肌细胞 Β3-AR Β受体拮抗剂 

分 类 号：R541.6[医药卫生—心血管疾病]