目的:观察胰岛素样生长因子1(IGF-1)是否可对抗低温保存诱导的心肌损伤,并探讨其可能的机制.方法:观察SD大鼠心脏低温保存9 h后,再灌注期左心室发展压(LVDP)和细胞凋亡指数的变化.Western blotting法检测蛋白激酶B(Akt)蛋白表达.结果:(1)Celsior保存液中加入10 nmol/L IGF-1可促进低温保存9 h后心脏收缩功能的恢复、减少心肌细胞凋亡的发生、抑制线粒体渗透性转换孔开放.(2)IGF-1可上调心脏Akt蛋白磷酸化水平.磷脂酰肌醇3-激酶(PI3K)特异性抑制剂LY294002不仅可降低IGF-1诱导的Akt磷酸化水平,且可逆转IGF-1促进低温保存心脏心功能的恢复和抗凋亡作用.(3)抑制热休克蛋白90(HSP90)可降低IGF-1诱导的Akt磷酸化和线粒体转位,阻断IGF-1的心肌保护作用.结论:IGF-1可明显减少低温保存心脏心肌细胞凋亡的发生,促进再灌注期心功能的恢复,其机制可能与HSP90依赖性Akt的激活和线粒体转位有关.%AIM: To investigate the effect of insulin - like growth factor 1 ( IGF - 1) on hypothermic preserva-tion of rat hearts. METHODS: Isolated rat hearts were preserved in Celsior solution with or without IGF -1(10 nmol/L) for 9 h, followed by 60 min of reperfusion. Cell apoptosis was assessed by TUNEL method. The left ventricular developed pressure ( LVDP) was recorded. Total Akt protein and phosphorylation of Akt protein were detected by Western blotting. RESULTS: Compared with Celsior solution preservation group, IGF - 1 significantly enhanced the LVDP recovery rate, decreased the apoptotic index, and inhibited the opening of mitochondrial permeability transition pore. IGF - 1 increased the phosphorylation of Akt in 9 h of hypothemically preserved rat heart, which was inhibited by PI3K inhibitor LY294002. LY294002 also abolished the cardioprotection of IGF - 1. 17 - Allylamino - 17 - demethoxy - geldanamycin, a heat -shock protein 90 ( HSP90) inhibitor, inhibited the IGF - 1 - induced increase in phosphorylation level of Akt and transola-tion to mitochondria, the improvement of cardiac functions, and the decrease in apoptosis. CONCLUSION: IGF - 1 im-proves the cardiac functions and decreases apoptosis in the hearts under hypothermic preservation. The mechanism might involve in HSP90 - dependent translocation in Akt to mitochondria.
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