【摘要】 目的:探讨缺血后处理对高胆固醇血症基础上发生的心肌缺血/再灌注损伤的影响及其可能的机制。方法:建立食源性高胆固醇血症大鼠模型,运用TTC染色、酶活性检测等方法测定缺血/再灌注所致的心肌损伤,用实时定量RT-PCR方法检测心肌组织中低氧诱导因子-1α(HIF-1α)mRNA水平,用Western blot方法检测HIF-1α蛋白水平。结果:高胆固醇血症加重了缺血/再灌注造成的心肌损伤,而缺血后处理显著缩小了高胆固醇血症大鼠缺血/再灌注所致的心梗面积,降低了血清肌酸激酶(CK)的活性,减少了心肌细胞凋亡。同时,缺血后处理提高了高胆固醇血症大鼠缺血心肌组织中HIF-1α的蛋白水平。结论:缺血后处理可以降低高胆固醇血症大鼠心肌对缺血/再灌注损伤的敏感性,其效应与心肌组织中HIF-1α的蛋白水平存在着相关性。更多还原

【Abstract】 Objective: To explore whether ischemic postconditioning can attenuate the myocardial injury induced by ischemia/reperfusion(I/R) in hypercholesteremic rats and whether hypoxia inducible factor-1α(HIF-1α) play a role in the protection.Methods: Adult male Wistar rats received a high fat diet for 8 weeks to prepare the hypercholesteremic models.Myocardial damage induced by ischemia/reperfusion was evaluated by infarct size,creatinkinase(CK) activity and myocardial apoptosis.HIF-1α mRNA level was detected by real time-RT-PCR and the protein level was detected by Western blot.Results: Myocardial infarct size,CK activity,and caspase-3 activity induced by I/R were markedly increased in hypercholesteremic rats compared with those in normal rats.Ischemic postconditioning attenuated the myocardial injury in both normal rats and hypercholesteremic rats,and increased HIF-1α protein level.There was a significant linear inverse relationship between HIF-1α protein level and infarct size(r=-0.802,P<0.01).Conclusion: Hypercholesteremia enhanced the susceptibility of myocardia to ischemia/reperfusion injury.While ischemic postconditioning markedly attenuated the increase of myocardial susceptibility to I/R induced by hypercholesteremia.HIF-1α might be one of the mechanisms of protection by ischemic postconditioning.更多还原