心力衰竭大鼠血清抗β_3肾上腺素能受体自身抗体的生物学效应  

Biological effects of the autoantibody against β_3-adrenoceptor from the sera of rats with heart failure

作　　者：李美霞[1] 张海峰[2] 张彦青[3] 贺忠梅[1] 刘晓军[4] 赵荣瑞[1] 刘慧荣[1] 

机构地区：[1]山西医科大学生理教研室,山西太原030001 [2]第四军医大学生理教研室,陕西西安710031 [3]山西医科大学第一医院,山西太原030001 [4]中国协和医科大学基础研究所,北京100005

出　　处：《中国病理生理杂志》2006年第12期2340-2344,共5页Chinese Journal of Pathophysiology

基　　金：山西省自然科学基金资助项目(No.20021103);山西医科大学基础医学院科研方向建设基金资助项目(No.20040708)

摘　　要：目的:建立心力衰竭大鼠模型,探讨心力衰竭发生发展过程与抗β3肾上腺素能受体(β3AR)细胞外第二环自身抗体产生的关系,并观察该抗体的生物学效应。方法:采用缩窄腹主动脉制备心力衰竭大鼠模型。(2)以人β3AR细胞外第二环的合成肽段作为抗原,采用ELISA检测心力衰竭大鼠血清中抗β3AR自身抗体。(3)提纯该抗体阳性的心力衰竭大鼠血清中的IgG。(4)设立各相应对照组观察该抗体对成年大鼠心肌细胞收缩效应和对乳鼠心肌细胞跳动频率的影响。结果:(1)心力衰竭大鼠模型在术前抗β3AR自身抗体呈低阳性率21.05%(4/19)、低滴度(平均滴度为1∶19.49);于术后12周该抗体呈高阳性率78.95%(15/19)、高滴度(平均滴度为1∶152.79)(与术前相比,P<0.01)。(2)该抗体可降低成年大鼠心肌细胞收缩和舒张效应,该作用不能被β1AR和β2AR受体拮抗剂(nadolol)阻断,但可被非特异性β受体拮抗剂(bupranolol)或β3抗原阻断。(3)该抗体可降低乳鼠心肌细胞跳动频率,同样该作用不能被nadolol阻断,但可被bupranolol或β3抗原阻断。此外,该抗体的负性变时效应在观察时间内(6 h)无衰减。结论:本研究首次证明心力衰竭模型形成过程中可产生较高滴度的抗β3肾上腺素能受体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力衰竭的病理生理机制。AIM： To investigate the relation between myocardial remodeling and the genesis of serum anti - β3 - adrenoceptor autoantibody, an animal model of heart failure （HF） was established and the biological effects of the autoantibody were observed. METHODS： （ 1 ） Healthy male Wistar rats were subjected to HF by constricting the abdominal aorta. （2） The anti - β3 - adrenoceptor autoantibody in the sera of HF rats was detected by ELISA with the synthetic peptide of the second extracellular loop of the β3 - adrenoceptor used as the antigen. （3） IgG in the positive sera from HF rats was prepared using a MabTrap Kit （Amersham）. （4） The effects of the autoantibody on the contractile response of adult isolated cardiomyocytes and on the beating rate of cultured neonatal rat cardiomyocytes were observed. RESULTS ： （ 1 ） The positive rate of anti β3 adrenoceptor autoantibody of rats increased from 21.05% of pretreatment to 78. 95% after heart failure （P 〈0. 01 ）. The antibody mean titer of rats increased from 1： 19. 49 ± 1.41 of pretreatment to 1： 152. 79 ±2. 89 after heart failure （P〈0. 01 ）. （2） The autoantibody against β3AR from HF rats reduced systolic and diastolic responses in adult isolated cardiomyocytes, which was not modified by pretreating myocytes with nadolol （ β1 AR and β2AR antagonist）,but was nearly prevented by bupranolol （nonselective β1 AR, β2AR and β3AR antagonist） or β3AR specific antigen. （3） The autoantibody decreased the beating rate in cultured neonatal rat cardiomyocytes, which persisted within 6 hours and was also not modified by pretreating myocyting with nadolol, but was nearly prevented by bupranolol or β3AR specific antigen. CONCLUSION： Our present study demonstrated that the higher titer of the autoantibody against β3 AR generated by myocardial remodeling process during HF, which induced negative inotropic and chronotropic effects, may be a possibility of involvement in the pathophysiological mechanisms leading to h

关 键 词：心力衰竭 充血性 受体 肾上腺素能Β 自身抗体 生物学效应 

分 类 号：R363[医药卫生—病理学]