Glucagon-like Peptide-1 (GLP-1), Immediately Prior to Reperfusion, Decreases Neutrophil Activation and Reduces Myocardial Infarct Size in Rodents
Glucagon-like Peptide-1 (GLP-1), Immediately Prior to Reperfusion, Decreases Neutrophil Activation and Reduces Myocardial Infarct Size in Rodents
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DOI：
10.1055/s-0031-1271777
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发表时间：
2011-05-01
影响因子：
2.2
通讯作者：
McDonagh, P. F.
中科院分区：
文献类型：
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作者：
Dokken, B. B.;La Bonte, L. R.;McDonagh, P. F.
胰升糖素样肽-1(GLP-1)是一种胰岛素，在包括心脏在内的多种组织中具有血糖调节和保护作用。我们推测GLP-1可能对心肌缺血后的中性粒细胞(PMN)有直接作用，从而减轻再灌注损伤。深麻醉SD大鼠左冠状动脉结扎30min，再灌流120min。在再灌注前立即给予GLP-1(人重组GLP-1，30 pm/kg/min)或PBS作为安慰剂。GLP-1显著降低心肌梗死范围[PBS(n=4)vs.GLP-1治疗动物(n=5)15.7+/-5.52%INF/AAR，p<；0.05]，体内PMN活化(fMLP刺激的CD11b表面表达：PBS 2.78+/-1.14 vs.GLP-11 1.7+/-0.21，TFI，p<；心肌蓄积(PBS：6.52+/-0.31 vs GLP-1：4.78+/-0.90，n=4-6只/组，p<；0.05)。此外，我们还发现GLP-1在体外降低了大鼠全血中PMN CD11b的表面表达，这种作用可被GLP-1受体阻断所抵消(PBS 6.52+/-0.31 vs GLP-1 4.78+/-0.90，TFI，p<；0.05)。这些结果提示，GLP-1减轻再灌注损伤的机制之一可能是减轻PMN介导的再灌注损伤。
Glucagon-like peptide-1 (GLP-1) is an incretin that has glucoregulatory effects as well as protective effects in a variety of tissues, including the heart. We hypothesized that GLP-1 may have a direct effect on neutrophils (PMNs) after myocardial ischemia, to ameliorate reperfusion injury. Deeply anesthetized Sprague-Dawley rats underwent 30 min of left coronary artery occlusion followed by 120 min of reperfusion. Immediately prior to reperfusion, rats were treated with either GLP-1 (human rGLP-1, 30 pM/kg/min) or PBS as placebo. GLP-1 significantly decreased myocardial infarct size [73.2 +/- 11.7% INF/AAR in PBS (n=4) vs. 15.7 +/- 5.52% INF/AAR in GLP-1-treated animals (n=5), p < 0.05], PMN activation in blood in vivo (fMLP-stimulated CD11b surface expression: PBS 2.78 +/- 1.14 vs. GLP-1 1.7 +/- 0.21, TFI, p < 0.05), and accumulation in myocardium (PBS: 6.52 +/- 0.31 vs. GLP-1: 4.78 +/- 0.90, n = 4-6 animals/group, p < 0.05). In addition, we found that GLP-1 mitigated PMN CD11b surface expression in whole rat blood in vitro, an effect that was abolished by GLP-1 receptor blockade (PBS 6.52 +/- 0.31 vs. GLP-1 4.78 +/- 0.90, TFI, p < 0.05). These findings suggest that one mechanism by which GLP-1 decreases reperfusion injury may be the attenuation of PMN-mediated reperfusion injury.