缺氧诱导因子1-α和染色体10缺失的磷酸酶与张力蛋白同源物基因在电刺激后兔缺血心肌组织中的表达及其意义  

Effects of direct current electric fields on the expressions of HIF 1-α and PTEN in ischemia myocardium of rabbit model

作　　者：张萍[1,2] 何国祥[1] 刘建平[1] 

机构地区：[1]第三军医大学西南医院心内科重庆市介入心脏病学研究所,重庆400038 [2]贵州省人民医院心内科,贵阳550002

出　　处：《临床心血管病杂志》2014年第11期1005-1009,共5页Journal of Clinical Cardiology

基　　金：国家自然科学基金资助(No:81170142)

摘　　要：目的:探讨缺氧诱导因子1-α(HIF 1-α)和染色体10缺失的磷酸酶与张力蛋白同源物基因(PTEN)在直流电刺激后兔急性心肌梗死(AMI)边缘区心肌组织中的表达及其对血管生成的作用。方法:95只日本大耳白兔,随机分为假手术组、AMI组、2.0V/cm电治疗(2.0EFs)组和4.0V/cm电治疗(4.0EFs)组。结扎冠状动脉左前降支建立AMI或假手术组模型后,在结扎血管两侧心外膜上缝合固定一对铂金电极,电治疗组直流电刺激,30min/d,分别治疗1d、3d、5d和1周、2周及4周。实验终点以Ⅷ因子免疫组织化学染色测定各实验组心肌组织中毛细血管密度,反转录聚合酶链(RT-PCR)检测心肌组织血管内皮细胞生成因子(VEGF)及HIF 1-α表达,免疫印迹分析(Western-blot)检测PTEN表达。结果:2.0EFs组及4.0EFs组治疗5d时毛细血管密度高于AMI组(F=41.291,P=0.000),该时相点心肌组织VEGF和HIF-1α表达较AMI组增加(F值分别为5.173、5.388;P值为0.024、0.021)、PTEN表达较AMI组下调(F=56.750,P=0.000),病理检查结果提示4.0EFs组梗死面积较AMI组减小(F=4.489;P=0.037)。结论:低压稳恒直流电场在一定作用时间内,通过下调缺血心肌组织PTEN的表达,刺激血管生成,缩小AMI面积。Objective：To observe the effects of steady direct current（DC）electric fields（EFs）with different intensity on the expressions of hypoxia-inducible factor-1α（HIF 1-α）and phosphatase and tensin homologue deleted from chromosome 10（PTEN）and the angiogenesis role in acute myocardial infarction（AMI）rabbit model.Method：The 95 rabbits were random divided into sham operation group（SH group）,control group（MI group）,2.0V/cm treatment group（2EFs group）and 4.0V/cm treatment group（4EFs group）.After the corresponding model was established,DC EFs（2.0V/cm or 4.0V/cm,30min/day）was given to the EFs group on 1day,3days,5days,1week,2weeks and 4weeks post-operation.The myocardial infarction areas,the capillary density,the expressions of vascular endothelial growth factor（VEGF）,HIF 1-αand PTEN in the ischemia myocardium were detected with pathomorphology and immunohistochemisty,reverse transcription polymerase chain reaction（RT-PCR）and Western-blot method.Result：The capillary density of the two EFs groups on 5days post-operation were higher than that of MI group（F=41.291;P=0.000）,meanwhile the expression of VEGF、HIF 1-αincreased accompany with expression of PTEN decreased on the same time point（F=5.173,5.388,56.750;P=0.024,0.021,0.000）.The myocardial infarction areas were also decreased after the 4.0V/cm EFs intervention compared with the MI group on 4weeks post-operation（F=4.489;P=0.037）.Conclusion：DC EFs can stimulate the angiogenesis in the ischemia myocardium through down-regulating the expression of PTEN by PTEN/phosphatidylinositol 3-kinase（PI3K）/Protein kinase B（Akt）/HIF-1α/VEGF pathway within a certain period of time,and thus improve the hemoperfusion in the ischemia area and diminish the myocardial infarction area.

关 键 词：直流电场 心肌梗死 血管生成 缺氧诱导因子1-Α 染色体10缺失的磷酸酶与张力蛋白同源物基因 

分 类 号：R542.2[医药卫生—心血管疾病]