抗β1肾上腺素能受体自身抗体介导PGC-1α在围产期心肌病中的作用及机制研究

Peripartum Cardiomyopthy（PPCM） is a form of heart failure that presents in the latter part of pregnancy or in the first 5 months postpartum. Our previous studies showed that autoantibodies against β1-adrenergic receptors (β1R-AABs) are detected in the serum of the patients with PPCM, another research demonstratrd that by causing cardiac angiogenic imbalance,the decrease of PGC-1α leads to PPCM. So that, we put forward the hypothesis that β1R-AABs may lead to PPCM by mediating the decrease of PGC-1α. We transferred sera of anti-β1-EC II-positive to healthy pregnant rat, use the immunology and molecular biology technology to develop our study at the overall level, the molecular level, the tissue level and cellular level as follow: 1. Study the correlation between β1R-AABs and cardiac function;2. Discuss the role of β1R-AABs on the expression of β1R and cardiomyocyte apoptosis; 3. Study the effect of β1R-AABs on myocardial PGC-1α and find a possible signaling pathways. This study may provide theoretical foundation and experimental basis for further study the pathogenesis of PPCM and find a predictive bio-marker and new way of therapy for PPCM.

围产期心肌病（PPCM）是发生于妊娠最后1个月及产后5个月间的心力衰竭，我们前期工作发现PPCM患者血清中存在高浓度的抗β1-受体自身抗体（β1R-AABs），另有国外研究表明PGC-1α生成减少，引起心脏血管生成失衡可导致PPCM的发生。据此我们提出假设β1R-AABs可通过介导PGC-1α生成减少导致PPCM。我们以β1R-AABs阳性血清免疫妊娠大鼠建立PPCM动物模型，运用免疫学、分子生物学等技术在整体水平、分子水平、组织水平及细胞水平进行如下研究：1.探究抗β1-受体自身抗体与PPCM发病的相关性及对心功能的影响；2.探究β1R-AABs对心肌细胞表面β受体表达及细胞凋亡的影响；3.进一步探讨β1R-AABs对心肌细胞PGC-1α的影响，对可能的信号转导通路进行研究。从而为进一步探讨PPCM的发病机制、寻找预测指标及新的治疗方法提供理论和实验依据。