低氧诱导因子-1Α参与低氧预处理诱导的心肌血管生成  

Hypoxia - inducible factor - la is involved in myocardial angiogenesis induced by hypoxic preconditioning

作　　者：李玉珍[1] 蔡莉蓉[1] 孙胜[1] 刘凤英[1] 刘秀华[1] 

机构地区：[1]解放军总医院基础所病理生理研究室,北京100853

出　　处：《中国病理生理杂志》2005年第12期2301-2304,共4页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(NO.30370569);解放军总医院科研基金资助项目(NO.01YM30)

摘　　要：目的:研究低氧诱导因子-1Α(HIF-1Α)在低氧预处理(HPC)诱导心肌血管生成中的作用,并探讨其细胞信号转导的机制。方法:雄性SD大鼠随机分为对照组和HPC组。动物置于低氧仓内,持续通入100% O2和 90％ N2 4H复制低氧预处理模型。用Ⅷ因子免疫组化染色检测HPC后7 D和21 D心肌组织微血管密度。制备心肌组织蛋白提取物,分别以磷酸化的细胞外信号调节激酶(ERK1/2)抗体和HIF-1Α抗体检测HPC后1 D、7 D和21 D P -ERK1/2活性及HIF-1Α表达。结果:HPC后7D和21D心肌组织微血管密度分别较对照组高36．99％和37．76％ (均P<0．01);P-ERK1/2活性在HPC后1D较对照组高18．67％;HPC诱导HIF-1Α的表达,其表达高峰出现在HPC 后1D。结论:HPC可以促进心肌微血管生成,其机制涉及ERKS活化和HIF-1Α表达上调。AIM： To investigate the relationship between the expression of hypoxia- inducible factor- 1α （HIF- 1α） and myocardial angiogenesis induced by hypoxic preconditioning （HPC）. METHODS： Male Sprague- Dawley rats were randomly divided into control group and hypoxic - preconditioned group. Rats in preconditioned group were subjected to hypoxic exposure （10% O2 and 90% N2） for 4 h, these rats were maintained in a normal environment respectively for 1 d, 7 d or 21 d. Then, vascular density was observed by the method of immunohistochemical staining with the antibody against factor Ⅶ - related antigen in rat myocardial tissue. Protein extracts of rat myocardial tissue were prepared for Western blotting analysis to measure the activities of extracellular signal - regulated protein kinases （ERKs） and HIF- 1α. RESULTS： In hypoxic- preconditioned group, microvascular density significantly increased in myocardial tissue. The expression of ERK1/2 increased by 18.67% at 1 d after HPC. HPC induced the expression of HIF - la, and the peak of expression was at first day after HPC. CONCLUSION： HPC promotes myocardial angiogenesis. Activation of ERKs and expression of HIF- 1α might be involved in myocardial angiogenesis induced by hypoxic preconditioning.

关 键 词：低氧诱导因子-1Α 低氧预处理 新生血管化 病理性 

分 类 号：R541.4[医药卫生—心血管疾病]