Charakterisierung der MBL (mannose binding lectin)-abhängigen Aktivierungen des Komplementsystems bei der myokardialen Ischämie- und Reperfusion (MI/R), der Rolle von C1q bei MI/R sowie Charakterisierung der Mechanismen MBL-abhängiger myokardialer Schädig

心肌缺血-再灌注（MI/R）是血管外科和心肌梗死中常见的临床问题。补体激活在与MI/R相关的局部和可能的远程组织损伤中起重要作用。来自我们实验室的最新证据表明，在体内阻断甘露糖结合凝集素（MBL）可防止补体的沉积和活化，导致MI/R 1-3后损伤显著减少和炎性基因表达减弱。使用C1 q（抑制经典途径）或MBL（抑制凝集素途径）或两者下游效应蛋白缺陷的小鼠，我建议确定导致实验性MI/R后组织破坏的事件。在这个提议中，我将研究MBL与C1 q（即l凝集素与经典途径）在MI/R后的作用。我推测MI/R后不可逆的心脏损伤依赖于MBL和凝集素补体途径的激活。具体目的如下：1）表征MI/R损伤的起始中MBL依赖性补体激活，并另外评估C1 q在MI/R中的作用; 2）确定MI/R后MBL依赖性损伤的机制。

Myocardial ischemia-reperfusion (MI/R) is a common clinical problem in the settings of vascular surgery and myocardial infarction. Complement activation plays an important role in local, and likely remote, tissue injury associated with MI/R. Recent evidence from our laboratory shows that blockade of mannose binding lectin (MBL) in vivo prevents deposition and activation of complement resulting in significantly reduced injury and attenduated inflammatory gene expression following MI/R 1-3. Using mice deficient in either C1q (inhibition of the classical pathway) or MBL (inhibition of the lectin pathway), or effector proteins downstream of both, I propose to identify the events leading to tissue destruction following experimental MI/R. In this proposal, I will investigate the role of MBL vs C1q (i.e.l lectin vs. classical pathway) following MI/R. I hypothesize that irreversible cardiac damage following MI/R is dependent on MBL and lectin complement pathway activation. The specific aims are as follows: 1) Characterize MBl-dependent complement activation in the initation of MI/R injury, and additionally evaluate the role of C1q in MI/R; 2) Determine the mechanism of MBL-dependent injury following MI/R.