Li Mei-xia, Wang Xiao-liang, Tang Jia-ning, Liu Xiao-jun, Tian Jue, Yan Li, Liu Hui-rong
Department of Physiology, Shanxi Medical University, Taiyuan 030001, China.
Zhonghua Xin Xue Guan Bing Za Zhi. 2005 Dec;33(12):1114-8.
To investigate the biological effects of anti-beta(3) adrenoceptor (beta(3)-AR) autoantibody in the serum of patients with heart failure, which may contribute to a new therapeutic clue for heart failure.
The synthetic peptide of the second extracellular loop of the beta(3)-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 cardiomyocytes were observed.
The positive rate of anti-beta(3)-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 beta(3)-AR from the patients group decreased cell shortening amplitude/cell shortening 3.84% +/- 0.33%, the velocity of shortening -0.47 microm/s +/- 0.07 microm/s and relengthening 0.17 microm/s +/- 0.02 microm/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 (beta(1)-AR and beta(2)-AR antagonist) in pretreating myocytes, but was nearly prevented by Bupranolol (nonselective beta-AR antagonist) or beta(3)-AR specific antigen.
It seems reasonable to state that a high titer of the autoantibody against beta(3)-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.
研究心力衰竭患者血清中抗β3肾上腺素能受体（β3-AR）自身抗体的生物学效应，为心力衰竭的治疗提供新线索。
以β3-AR第二个细胞外环的合成肽为抗原，采用酶联免疫吸附试验筛选心力衰竭患者和健康对照者的血清。按照制造商的说明，使用MabTrap试剂盒（Amersham）制备阳性自身抗体血清患者组中的IgG。观察每组IgG对成年离体心肌细胞收缩反应和培养的新生大鼠心肌细胞搏动频率的影响。
心力衰竭患者和健康受试者抗β3-AR自身抗体的阳性率分别为26.7%（平均抗体滴度：1:43.27±2.71）和11.0%（平均抗体滴度：1:14.59±1.61），P<0.05。与对照组相比，患者组抗β3-AR自身抗体使成年离体心肌细胞的细胞缩短幅度/细胞缩短率分别降低3.84%±0.33%、缩短速度降低0.47μm/s±0.07μm/s、再伸长速度降低0.17μm/s±0.02μm/s。患者组自身抗体使培养的新生大鼠心肌细胞的搏动频率降低47.1次/分钟±8.11次/分钟，且可持续6小时。预先用纳多洛尔（β1-AR和β2-AR拮抗剂）处理心肌细胞并不能改变这种降低，但用布普洛尔（非选择性β-AR拮抗剂）或β3-AR特异性抗原处理可几乎完全阻止这种降低。
心力衰竭患者血清中高滴度的抗β3-AR自身抗体具有负性变力和变时作用，可能是心力衰竭病理生理机制的一部分，这一说法似乎合理。
