The effect of C1 inhibitor on myocardial ischemia and reperfusion injury.
The effect of C1 inhibitor on myocardial ischemia and reperfusion injury.
复制标题
DOI：
10.1016/j.carpath.2012.05.003
复制
发表时间：
2013-01
影响因子：
3.7
通讯作者：
Davis, Alvin E., III
中科院分区：
文献类型：
--
作者：
Lu, Fengxin;Fernandes, Stacey M.;Davis, Alvin E., III
补体系统的激活已被证明是介导心肌缺血和再灌注（MIR）损伤的重要机制。C1抑制剂（C1 INH）已被证明是有益的实验MIR模型。这种效应的潜在机制被认为主要是由于抑制补体系统激活。我们最近证明，C1 INH在小鼠肠缺血和再灌注模型中抑制白细胞迁移中起直接作用。本研究的目的是探讨C1 INH在小鼠MIR模型中的有益作用的机制。将C57 BL/6、C1 INH-/-和C3-缺陷小鼠（C3-/-）进行冠状动脉左前降分支（LAD）阻断30 min（C57 BL/6和C1 INH-/-）或60 min（C3-/-），然后再灌注4 h。再灌注前5 min静脉注射C1 INH或反应中心裂解的失活C1 INH（iC 1 INH）。与溶剂处理的小鼠相比，C1 INH处理的WT、C1 INH-/-和C3-/-小鼠中相对于风险区域或相对于左心室区域的心肌梗死面积显著减小。在溶剂处理的MIR小鼠中，MIR诱导心肌多形核白细胞积聚和血浆心脏特异性肌钙蛋白I水平增加，而C1 INH处理显著减弱这些作用。iC 1 INH具有类似的保护作用。这些结果表明，C1 INH防止了小鼠MIR损伤，并且这种心脏保护作用可能不仅仅是由补体抑制引起的，还可能是通过抑制白细胞募集到缺血组织中而产生的，这种作用不是通过蛋白酶抑制介导的。
Activation of the complement system has been demonstrated to be an important mechanism in the mediation of myocardial ischemia and reperfusion (MIR) injury. C1 inhibitor (C1INH) has been shown to be beneficial in experimental MIR models. The underlying mechanism of this effect has been assumed to result primarily from inhibition of complement system activation. We recently demonstrated that C1INH plays a direct role in suppression of leukocyte transmigration in the mouse intestinal ischemia and reperfusion model. The purpose of this study was to investigate the mechanism of the beneficial effect of C1INH in mouse MIR model. C57BL/6, C1INH-deficient (C1INH-/-) and C3-deficient mice (C3-/-) were subjected to 30 min (C57BL/6 and C1INH-/-) or 60 min (C3-/-) occlusion of the left anterior descending branch (LAD) of the coronary artery followed by 4h reperfusion. C1INH or reactive center cleaved inactive C1INH (iC1INH) was injected intravenously 5min before reperfusion. Myocardial infarct size relative to the area at risk or relative to left ventricular area was significantly reduced in C1INH treated WT, C1INH-/- and C3-/- mice compared with vehicle-treated mice. MIR induced an increase in myocardial polymorphonuclear neutrophil accumulation and plasma cardiac specific troponin I levels in vehicle-treated MIR mice while C1INH treatment significantly attenuated these effects. iC1INH had a similar protective effect. These results suggested that C1INH prevented MIR injury in mice and that this cardioprotective effect may not solely result from complement inhibition, but might be also contributed by inhibiting leukocyte recruitment into ischemic tissue, an effect that is not mediated via protease inhibition.
登录
查看更多内容
影响因子：
4.4
作者：
Cai, SH;Dole, VS;Davis, AE
通讯作者：
Davis, AE
影响因子：
4.4
作者：
Buerke, M;Schwertz, H;Darius, H
通讯作者：
Darius, H
DOI：
10.1084/jem.133.4.885
发表时间：
1971-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hill JH;Ward PA
通讯作者：
Ward PA
影响因子：
3.6
作者：
Gorsuch, W. Brian;Guikema, Benjamin J.;Stahl, Gregory L.
通讯作者：
Stahl, Gregory L.
影响因子：
37.8
作者：
BUERKE, M;MUROHARA, T;LEFER, AM
通讯作者：
LEFER, AM