心梗后心衰患者小窝蛋白Caveolin-3对SCD的预测价值及其机制研究

The prevention of sudden cardiac death (SCD) in patients with heart failure after myocardial infarction is the worldwide problem to be solved. At present, seeking an effective predictor of high-risk patients for risk stratification and prognosis of SCD is the hot spot in this field. On the basis of preliminary work and the latest research progress, the applicant has firstly proposed that, the in vivo inflammation and oxidative stress during the development of heart failure after myocardial infarction leads to the caveolin-3down-regulation in the plasma membrane of cardiomyocytes,therefor disturbed the balance of ion channels and signal transductionhomostasis,which formed the key mechanism of SCD. This programaim to explore the specific correlation between the down-regulation and redistribution of caveolin-3 in the plasma membrane of cardiomyocytes, and the association between the skeletal muscle and the myocardial membrane in the caveolin-3 expression localized at the plasma during the deterioration of heart failure after myocardial infarction. Finally,by detecting the caveolin-3 plasma expression in skeletal muscle and cardiomyocytesin patients who schedule to undergo the CRT/CRTD or pacemaker implantation in our hospital. Based on the caveolin-3 expression and some clinical incidence we would establish the risk stratification project of SCD. This program will provide scientific evidence on searching a new clinical biological indicator for the high-risk SCD patients and eventually establish the risk stratification of SCD in clinical practice by thoracic muscle biopsy. Additionally we will propose a more effective standard of risk stratification of SCD.

心梗后心衰患者心脏性猝死的预防是全世界范围内亟待解决的课题。寻求有效的高危预测指标对患者进行危险分层和预后判断是SCD领域的研究热点。申请人在前期工作的基础上，结合最新的研究进展，首次提出：心梗后心衰时炎症、氧化应激的打击导致心肌细胞膜小窝蛋白Caveolin-3下调，致其所调控的离子通道、信号转导系统失衡是导致SCD发生与发展的关键环节。本项目拟从细胞、动物及临床三方面探讨:(1)心梗后心衰时心肌细胞膜Caveolin-3下调与SCD的特异性关联；(2)心梗后心衰时骨骼肌细胞膜Caveolin-3的表达与心肌细胞膜Caveolin-3表达的关联程度；（3）临床入选拟行CRT和永久性起搏器植入术的心梗后心衰患者，检测植入部位胸肌Caveiolin-3的表达并结合临床指标制定SCD危险分层的预测方案。本研究将为临床上潜在高危SCD患者的早期识别和危险分层及新的SCD干预靶点研究提供科学依据。

心肌梗死后心衰时，炎症、氧化应激等导致心肌细胞膜小窝蛋白Caveolin-3下调，进而导致其所控制的离子通道、信号转导系统失衡，导致心脏性猝死（SCD）的发生。本课题申请人长期从事SCD的发生机制，流行病学和综合防治方面的研究工作。在既往工作基础上，本研究拟通过心梗后心衰大鼠的心肌细胞Caveolin-3 表达水平探索其与SCD的关联性；研究迷走神经刺激对心肌梗死后心衰大鼠Caveolin-3表达的影响和机制，探讨其能否成为有效预防SCD的新方法。本研究将为临床上潜在的高危SCD患者的早期识别和危险分层，以及新的SCD干预靶点研究提供依据。