缺血后处理降低高胆固醇血症大鼠心肌对缺血/再灌注损伤的易感性及其机制  

The attenuation of myocardial susceptibility to ischemia/reperfusion injury by ischemic postconditioning in hypercholesteremia rats and the role of hypoxia inducible factor-1α

作　　者：赵焕新[1] 李晓宇[2] 武烨[2] 王晓樑[2] 赵荣瑞[2] 刘慧荣[3] 

机构地区：[1]山西中医学院生理教研室,太原030024 [2]山西医科大学,太原030001 [3]首都医科大学生理学与病理学系,北京100069

出　　处：《中国应用生理学杂志》2012年第4期319-322,327,共5页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金青年项目(81100150)

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。Objective： To explore whether ischemic postconditioning can attenuate the myocardial injury induced by ischemia/reperfusion （I/R） in hypercbelesteremic 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 beth 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： Hypercbelesteremia enhanced the susceptibility of myocardia to ischemia/reperfusion injury. While ischemic postconditioning markedly attenuated the increase of myocardial susceptibility to I/R induced by hypercbelesteremia. HIF-1α might be one of the mechanisrm of protection by ischemic postconditioning.

关 键 词：缺血后处理 高胆固醇血症 低氧诱导因子-1 心肌缺血 

分 类 号：R331[医药卫生—人体生理学]