Single dose GLP-1-Tf ameliorates myocardial ischemia/reperfusion injury.
Single dose GLP-1-Tf ameliorates myocardial ischemia/reperfusion injury.
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DOI：
10.1016/j.jss.2009.03.016
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发表时间：
2011-01
期刊：
影响因子：
--
通讯作者：
Gorman RC
中科院分区：
文献类型：
--
作者：
Matsubara M;Kanemoto S;Leshnower BG;Albone EF;Hinmon R;Plappert T;Gorman JH 3rd;Gorman RC
胰高血糖素样肽-1 （GLP-1）具有拟胰岛素、促胰岛素和抗凋亡的特性，可能使其成为心肌梗死（MI）再灌注治疗的有用辅助药物；然而，GLP-1的血浆半衰期很短。GLP-1与人转铁蛋白（GLP-1- tf）融合可显著延长药物半衰期。我们检测了单剂量GLP-1-Tf对家兔心肌缺血（30分钟）/再灌注（180分钟）损伤的抑制作用。19只动物作为未经处理的对照。缺血前组（n=10）在缺血前12小时给予GLP-1-Tf 10mg/kg。再灌注后立即缺血组（n=10）给予GLP-1-Tf (10mg/kg)， Tf组（n=4）单独给予转铁蛋白。对照组、缺血前组、缺血后组和Tf组梗死面积占危险面积的比例分别为59.1±1.3%、45.7±1.9%、44.1±3.3%、59.7±2.0% （GLP-1-Tf治疗组与对照组相比p<0.05）。GLP-1-Tf使凋亡指数从对照组的4.67±0.40%降低到缺血前组的3.15±0.46%，缺血后组的2.66±0.40%（与对照组相比，GLP-1-Tf处理均<0.05）。缺血后组壁运动异常大小和射血分数较对照组明显改善。缺血后组血清GLP-1水平为239.8±25.7µg/ml，缺血前组为27.9±5.8µg/ml，对照组未检出。GLP-1-Tf限制心肌再灌注损伤，无论是在缺血发作前还是在再灌注时给予。GLP-1-Tf也可能限制高血清药物水平下的心肌昏迷。
Glucagon-like peptide-1 (GLP-1) has insulinomimetic, insulinotropic and antiapoptotic properties that may make it a useful adjunct to reperfusion therapy for myocardial infarction (MI); however, GLP-1 has a short plasma half-life. Fusion of GLP-1 to human transferrin (GLP-1-Tf) significantly prolongs drug half-life. We tested the ability of single dose GLP-1-Tf to limit myocardial ischemia (30 minutes) /reperfusion (180 minutes) injury in rabbits. Nineteen animals were untreated controls. The pre-ischemic group (n=10) was given 10mg/kg of GLP-1-Tf 12 hours before ischemia. Immediately after reperfusion, the post-ischemic group (n=10) received GLP-1-Tf (10mg/kg) and the Tf group (n=4) received transferrin alone. Infarct size as a percentage of the area at risk was 59.1 ± 1.3%, 45.7 ± 1.9%, 44.1 ± 3.3%, 59.7 ± 2.0% in the control group, pre-ischemic group, post-ischemic group and Tf group, respectively (p<0.05 for both GLP-1-Tf treatments group vs. control). GLP-1-Tf reduced the apoptotic index from 4.67 ± 0.40% in the control group to 3.15 ± 0.46% in the pre-ischemic group and to 2.66 ± 0.40% in the post-ischemic group (p<0.05 for both GLP-1-Tf treatments vs. control). The size of the wall motion abnormality and ejection fraction was significantly improved in the post-ischemic group relative to the control group. Serum GLP-1 levels were 239.8 ± 25.7µg/ml in the post-ischemic group, 27.9 ± 5.8µg/ml in the pre-ischemic group and undetectable in the control group. GLP-1-Tf limits myocardial reperfusion injury whether given prior to the onset of ischemia or given at reperfusion. GLP-1-Tf may also limit myocardial stunning at high serum levels of the drug.
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影响因子：
3
作者：
Kavianipour, M;Ehlers, MR;Gutniak, M
通讯作者：
Gutniak, M
DOI：
10.1152/ajpheart.01081.2004
发表时间：
2005-06-01
影响因子：
4.8
作者：
Bopassa, JC;Michel, P;Ferrera, R
通讯作者：
Ferrera, R
影响因子：
5
作者：
Mocanu, MM;Bell, RM;Yellon, DM
通讯作者：
Yellon, DM
影响因子：
20.1
作者：
Tong, HY;Chen, WN;Murphy, E
通讯作者：
Murphy, E
影响因子：
8.2
作者：
Buteau, J;Roduit, R;Prentki, M
通讯作者：
Prentki, M