Caveolae-Gαq-PLCβ信号通路在压力负荷诱导心肌肥厚中的机制研究

压力负荷诱导的心肌肥厚是临床上的一种常见疾病，但其发生发展机制尚不完全清楚。我们在前期的体外实验研究中发现，牵张刺激可破坏细胞膜表面Caveolae结构，增加细胞膜表面Caveolin蛋白与Gαq蛋白间距离，进而特异性影响细胞内Gαq-PLCβ信号通路的反应。在此基础上，我们以主动脉缩窄（Transverse Aortic Constriction,TAC）模型小鼠为研究对象，采用生物化学，分子生物学和生物物理学等研究手段，研究Caveolae-Gαq-PLCβ信号通路相关分子在TAC后小鼠心肌细胞内的时空变化特点，分析其与TAC后心肌形态和功能改变的相关性，并探讨Caveolae-Gαq相互作用的可能分子机制，为进一步阐明压力负荷诱导心肌肥厚的具体机制，寻找有效的预防和逆转其发生发展的药物提供一定实验依据和理论基础。

Pressure overload-induced cardiac hypertrophy is a common clinical disease, but the underlying mechanisms are still unclear. In our previous in vitro study, we found that stretch could deform the structures of caveolae, increase the distance between Caveolin and Gαq on cell membrane, and specifically affect the intracellular Gαq-PLCβ signal pathway. Based on these previous results, we intend to use the mouse model of transverse aortic constriction (TAC) in this study. Through the methods of biochemistry, molecular biology and biophysics, we try to observe the spatiotemporal changes of Caveolae-Gαq-PLCβ signal pathway in mouse cardiomyocytes after TAC surgery, analyze their relevance to cardiac morphological and functional changes after TAC, and investigate the probable molecular mechanisms of Caveolae-Gαq interaction. Through this project, we could provide some new experimental data and research basis for the mechanisms research of pressure overload-induced cardiac hyptertrophy, and the exploring the effective drugs for preventing and reversing the hypertrophic response.