Anti-ischemia/reperfusion of C1 inhibitor in myocardial cell injury via regulation of local myocardial C3 activity
Anti-ischemia/reperfusion of C1 inhibitor in myocardial cell injury via regulation of local myocardial C3 activity
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DOI：
10.1016/j.bbrc.2006.09.023
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发表时间：
2006-11-10
影响因子：
3.1
通讯作者：
Liu, Dongxu
中科院分区：
文献类型：
--
作者：
Fu, Jinrong;Lin, Guosheng;Liu, Dongxu
C3在补体激活增强缺血/再灌注（I/R）诱导的心肌损伤和心功能障碍的所有途径中都是常见的。补体调节蛋白C1抑制剂（C1INH）的补体抑制作用具有明显的心脏保护作用。在这里，我们研究了C1INH是否调节缺血心肌组织中的C3活性。C1INH在I/ r诱导的大鼠急性心肌梗死（AMI）模型和培养的大鼠H9c2心肌细胞中均能显著抑制C3 mRNA表达和蛋白合成。至少，这种调控是在转录水平上对氧张力的响应。在体外实验中，C3在大鼠心肌细胞表面的沉积和结合被C1INH显著阻断。C1INH可以通过抑制C3的生物活性来抑制经典补体介导的细胞裂解。因此，C1INH除了抑制全身补体激活外，还通过直接抑制局部心肌C3活性来防止心肌细胞损伤。(c) 2006爱思唯尔公司版权所有。
C3 is common to all pathways of complement activation augmenting ischemia/reperfusion (I/R)-induced myocardial injury and cardiac dysfunction. Complement inhibition with the complement regulatory protein, C1 inhibitor (C1INH), obviously exerts cardioprotective effects. Here, we examine whether C1INH regulates C3 activity in the ischemic myocardial tissue. C1INH markedly suppressed C3 mRNA expression and protein synthesis in both a model of I/R-induced rat acute myocardial infarction (AMI) and the cultured rat H9c2 heart myocytes. At least, this regulation was at the transcriptional level in response to oxygen tension. In vitro, C3 deposition on, and binding to, the surface of rat myocardial cells were significantly blocked by C1INH treatment. C1INH could inhibit classical complement-mediated cell lysis via suppressing the biological activity of C3. Therefore, C1INH, in addition to inhibition of the systemic complement activation, prevents myocardial cell injury via a direct inhibitory role in the local myocardial C3 activity. (c) 2006 Elsevier Inc. All rights reserved.