蛋白激酶D1促血管新生的体内外实验分析  

Promoting angiogenesis of protein kinase D1 in vitro and in vivo

作　　者：杨雷[1] 刘暖[1] 毛秉豫[1] 徐国昌[1] 叶松山[1] 张培华[1] 张瓅方[1] 

机构地区：[1]南阳理工学院医学实验中心,河南南阳473004

出　　处：《中国病理生理杂志》2016年第1期146-150,155,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81473438;No.81202791);河南省中医内科学重点学科支撑课题(豫教高[2012]186号)

摘　　要：目的:探讨蛋白激酶D1(PKD1)促血管新生的作用,为心肌梗死等缺血性疾病以PKD1为治疗靶点提供新的思路。方法:体外培养、分离和鉴定内皮祖细胞(EPCs),观察PKD1及其特异性阻断剂CID755673对EPCs中血管内皮生长因子(VEGF)及其受体KDR表达的影响。复制大鼠心肌梗死模型,分析PKD1及CID755673干预对大鼠心肌梗死后受损心肌组织病理形态学、微血管和内皮细胞变化以及VEGF、KDR表达的影响。结果:EPCs体外细胞培养实验表明,PKD1可明显上调EPCs中VEGF和KDR的表达水平。大鼠心肌梗死动物实验结果表明,PKD1干预后的大鼠心肌组织排列较为有序,结构较为清晰,内皮细胞胞膜光滑、完整,周细胞可见,心肌组织中的VEGF和KDR表达水平显著上调。结论:PKD1有明显的促血管新生作用,该作用可能是通过VEGF介导而实现的。AIM： To explore the effect of protein kinase D1（ PKD1） on promoting angiogenesis in vitro and in vivo,and to furnish a new idea on targeting PKD1 for the treatment of ischemic heart disease such as myocardial infarction.METHODS： The culture,isolation and identification of endothelial progenitor cells（ EPCs） were performed in vitro. The effects of PKD1 and its specific blocking agent CID755673 on expression levels of vascular endothelial growth factor（ VEGF） and kinase insert domain receptor（ KDR） in EPCs were determined. The rat model of myocardial infarction was established,the intervention effects of PKD1 and CID755673 on morphology,changes of microvessels and endothelial cells,and the expression of VEGF and KDR in the impaired myocardial tissue were analyzed. RESULTS： PKD1 significantly upregulated the expression of VEGF and KDR in EPCs in vitro. Meanwhile,the structure of myocardial tissue was more regular and clear,the cytomembrane of endothelial cells were more smooth and integrity,the pericytes were visible,and the expression of VEGF and KDR was significantly increased in PKD1 treatment group in vivo. CONCLUSION： PKD1 has the ability of angiogenesis obviously,which might be mediated by VEGF.

关 键 词：蛋白激酶D1 心肌梗死 血管新生 内皮祖细胞 血管内皮生长因子 

分 类 号：R363[医药卫生—病理学]