流体切应力对内皮祖细胞内皮型一氧化氮合酶基因表达和一氧化氮分泌的影响  

Fluid shear stress upregulated endothelial nitric oxide synthase gene expression and nitric oxide formation in human endothelial progenitor cells

作　　者：杨震[1] 陶军[1] 王洁梅[1] 涂昌[1] 徐明国[1] 王妍[1] 陈龙[1] 罗初凡[1] 唐安丽[1] 马虹[1] 

机构地区：[1]中山大学附属第一医院心内科,广州510080

出　　处：《中华心血管病杂志》2007年第4期359-362,共4页Chinese Journal of Cardiology

基　　金：国家自然科学基金(30470475)

摘　　要：目的本研究旨在观察不同切应力对内皮祖细胞内皮型一氧化氮合酶(eNOS)基因表达和一氧化氮(NO)分泌的影响,以探讨流体切应力对内皮祖细胞功能的调节作用。方法诱导健康成人外周血的单个核细胞分化为内皮祖细胞,分为静态组、低切应力组(5 dyn/cm^2,1 dyn/cm^2=0.1Pa)、中切应力组(15 dyn/cm^2)和高切应力组(25 dyn/cm^2)4个不同处理组,观察不同切应力对内皮祖细胞 eNOS 基因表达和 NO 分泌的影响。结果外周血单个核细胞分化成为内皮祖细胞,倒置荧光显微镜下呈典形的"纺锤样"梭形细胞,ac-LDL 吞噬及 lectin 抗体荧光标记双阳性,FLK-1和 vWF免疫荧光抗体染色均为阳性。切应力处理4 h,低、中和高切应力组内皮祖细胞 eNOS/β-肌动蛋白基因表达比值分别为0.364、0.505和0.548,较静态组(0.183)明显高(P<0.05)。在切应力处理的各时间点,低、中和高切应力组内皮祖细胞 NO 分泌也较静态组明显升高(P<0.05)。结论流体切应力提高明显上调内皮祖细胞 eNOS 基因表达和促进其 NO 分泌,提示流体切应力可改善内皮祖细胞的功能活性,是提高内皮祖细胞修复血管内皮损伤能力的有效方法之一。Objective To observe the effect of fluid shear stress on the eNOS gene expression and NO production in endothelial progenitor cells （EPCs）. Methods The peripheral blood mononuclear cells from healthy volunteers were inducted into EPCs and divided into stationary group （0 dyn/cm^2, 1 dyn/cm^2 =0. 1Pa）, low-flow shear stress group（5 dyn/cm^2）, medium-flow shear stress group （15 dyn/cm^2） and high-flow shear stress group （25 dyn/cm^2 ）. The effects of shear stress on the endothelial nitric oxide synthase （eNOS） gene expression and nitric oxide （NO） production in human EPCs were measured. Results Typical ＂spindle-shaped＂ appearance was shown in EPCs derived from peripheral blood mononuclear cells and were positively labeled by acetylated-LDL, lectin, FLK-1 and vWF. After 4 hours treatment with various shear stresses, the ratio of eNOS/β-actin mRNA expression by human EPCs in low, medium and high-flow shear stress group was 0. 364, 0. 505 and 0. 548 respectively, which was significantly higher than that in stationary group （0. 183, all P 〈0. 05） and the NO secretion in human EPCs in low, medium and high-flow shear stress group was also signiticanfly higher than that in stationary group （ all P 〈 0.05 ）. Conclusion Fluid shear stress enhances the eNOS mRNA expression and NO secretion in human EPCs, therefore, shear stress could potentiate the repair efficacy of EPCs for endothelial injury.

关 键 词：动脉硬化 干细胞 血流动力学 一氧化氮合酶 一氧化氮 

分 类 号：R541.4[医药卫生—心血管疾病]