Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts.
Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts.
复制标题
胰岛素样生长因子-1 可改善肥厚心脏的缺血后恢复。
DOI：
10.1016/s0003-4975(01)03098-3
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
delNido,PJ
中科院分区：
文献类型：
--
作者：
Friehs,I;Stamm,C;Cao-Danh,H;McGowan,FX;delNido,PJ
背景：与正常心脏相比，严重心肌肥大与缺血耐受性降低有关。我们假设胰岛素样生长因子-1 （IGF-1）治疗通过增加缺血和早期再灌注期间的葡萄糖摄取来改善缺血后心肌恢复。方法10日龄家兔胸主动脉捆扎造成压力超负荷肥厚。在5周龄（严重肥厚）时，主动脉束带和假手术离体心脏在缺血前灌注和心脏停跳中伴或不伴IGF-1进行30分钟的恒温缺血，然后再灌注30分钟。结果2-脱氧葡萄糖摄取（31P-NMR）和磷脂酰肌醇-3-激酶（pi -3-激酶）活性显著降低。胰岛素样生长因子-1恢复葡萄糖摄取和pi -3激酶活性，以控制肥大心脏的水平，这两种作用都被wortmannin（一种pi -3激酶抑制剂）阻断。与未处理或IGF-1+沃特曼宁处理的肥厚心脏相比，IGF-1处理的心脏缺血后发育压力显著改善。结论IGF-1可改善肥厚心脏的葡萄糖摄取和缺血耐受性。心肌IGF-1效应可能是通过pi -3激酶依赖途径介导的。
BackgroundSevere myocardial hypertrophy is associated with decreased tolerance to ischemia compared with normal hearts. We hypothesized that treatment with insulin-like growth factor-1 (IGF-1) improves postischemic myocardial recovery by increasing glucose uptake during ischemia and early reperfusion.MethodsBanding of the thoracic aorta in 10-day-old rabbits created pressure-overload hypertrophy. At 5 weeks of age (severe hypertrophy), aortic banded and sham-operated isolated hearts underwent 30 minutes of normothermic ischemia with or without IGF-1 in the preischemic perfusate and cardioplegia followed by 30 minutes of reperfusion.Results2-Deoxyglucose uptake (31P-NMR) and phosphatidylinositol-3-kinase (PI-3-kinase) activity were significantly lower in hypertrophied hearts. Insulin-like growth factor-1 restored glucose uptake and PI-3-kinase activity to control levels in the hypertrophied hearts and both effects were blocked by wortmannin (a PI-3-kinase inhibitor). Postischemic developed pressure was significantly improved in IGF-1-treated hearts compared with untreated or IGF-1+wortmannin-treated hypertrophied hearts.ConclusionsThese data indicate that IGF-1 improves glucose uptake and tolerance to ischemia in hypertrophied hearts. Myocardial IGF-1 effects are likely mediated through a PI-3-kinase-dependent pathway.