心室颤动(室颤)是心肌梗死后心脏性猝死最常见的心律失常之一。研究表明，心肌梗死后交感神经重构是室颤发生和维持的重要原因，但其具体分子机制仍不明确。最近的研究表明，交感神经和谷氨酸及其受体有一定的相关性。本项目综合国内外的研究现状，在深入分析心肌梗死后室颤发生机制、交感神经与谷氨酸及其受体关系的基础上，提出了Ⅰ型代谢型谷氨酸受体（mGluR1/5)是心肌梗死后交感神经重构致室颤发生和维持的分子基础的假说。拟通过建立犬心肌梗死和心肌梗死后室颤模型，利用分子生物学及现代电生理学技术，研究mGluR1/5通过其信号转导通路调控膜蛋白及相关离子通道促进室颤发生和维持的机制；并利用RNA干扰技术，探讨特异性沉默mGluR1/5预防室颤发生的可能性。这些研究结果将促进对mGluR1/5生物学功能的认识，有助于进一步揭示心肌梗死后室颤发生和维持的触发与基质因素，从而为更好地防治室颤提供新的理论依据和策略。

Ventricular fibrillation (VF) is one of the most common arrhythmias for sudden cardiac death after myocardial infarction (MI). Sympathetic nerve remodeling (SNR) after MI has been shown to be responsible for the lethal arrhythmias such as VF. However, no exact mechanisms, especially molecular mechanisms have yet explained how VF is triggered and maintained by SNR. Recent studies have demonstrated that there were relationships between sympathetic nerve (SN) and glutamate and its receptors. Based on the mechanisms of occurrence of VF after MI and the relationships between SN and glutamate and its receptors, we hypothesize that group I metabotropic glutamate receptors (mGluRs) including mGluR1 and mGluR5 (mGluR1/5) is one of the molecular mechanisms that lead to the occurrence and maintenance of VF induced by SNR after MI. MI and post-MI VF models of dogs will be established and modern molecular biology and electrophysiological techniques will be used in the present project to study the specific mechanisms of mGluR1/5 leading to the occurrence and maintenance of VF, including the signal transduction pathways that regulate the membrane proteins and related ion channels. Meanwhile, the technique of RNA interference will be used to verify the preventive role of the gene silence of mGluR1/5 for VF. These findings will contribute to the understanding of the biological functions of mGluR1/5 and reveal the elements of trigger and matrix for VF after MI, so as to provide new theoretical basis and strategies for the better prevention and treatment of VF after MI.