脱氢表雄酮对血管内皮细胞损伤后单核细胞与内皮细胞相互作用的影响  

Effects of dehydroepiandrosterone on the interaction between endothelial cells and monocytes after endothelial cell injury

作　　者：郝群[1] 梁元姣[1] 张承[1] 李大金[2] 汪灏[3] 

机构地区：[1]南京军区南京总医院妇产科,南京医学博士210002 [2]复旦大学附属妇产科研究所,上海200011 [3]南京大学医学院附属鼓楼医院普通外科,南京210008

出　　处：《医学研究生学报》2012年第6期571-576,共6页Journal of Medical Postgraduates

基　　金：国家自然科学基金(30400353)

摘　　要：目的脱氢表雄酮(dehydroepiandrosterone,DHEA)是成人体内最为丰富的来源于肾上腺的甾体激素,文中探讨DHEA对氧化型低密度脂蛋白(oxidized low density lipoprotein,ox-LDL)所致血管内皮细胞损伤后单核细胞与内皮细胞相互作用的影响。方法以培养的人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)作为靶细胞,在内皮细胞培养基中加入ox-LDL或在试验体系中加入不同浓度的DHEA,测定人单核细胞系U937与HUVEC的黏附,检测内皮细胞条件培养基中一氧化氮(nitric oxide,NO)及单个核细胞趋化蛋白-1(monocyte chemoattractant protein,MCP-1)的含量,应用流式细胞仪检测内皮细胞表面黏附分子细胞间黏附分子-1(intercellular adhesion molecule-1,ICAM-1)、血管细胞黏附分子-1(vascularcell adhesion molecule-1,VCAM-1)及E-选择素的表达。将内皮细胞条件培养基作用于U937细胞,应用RT-PCR检测U937细胞CCR2、LFA-1以及VLA-4 mRNA的表达。结果 DHEA可明显抑制单核U937细胞与内皮细胞之间的相互黏附,明显促进内皮细胞NO合成,抑制MCP-1分泌,降低内皮细胞表面ICAM-1、VCAM-1的表达,且经DHEA作用后的内皮细胞条件培养基可明显抑制单核U937细胞CCR2、淋巴细胞功能相关抗原(lymphocyte function-associated antigen,LFA)-1以及非常晚期抗原(very late antigen,VLA)-4 mRNA的表达。结论 DHEA可通过抑制内皮细胞分泌趋化因子、下调内皮细胞表面黏附分子的表达,抑制内皮细胞对单核细胞的趋化及相互黏附,据此认为DHEA可能对血管内皮细胞具有保护作用。Objective Dehydroepiandrosterone （DHEA） is the most abundant steroid secreted by adrenal glands in adults. This study was to investigate the effect of DHEA on the interaction between endothelial ceils and monocytes after endothelial cell injury in-dueed by oxidized low-density lipoprotein （ox-LDL）. Methods Using cultured human umbilical vein endothelial cells （HUVECs） as target cells, we added ox-LDL to the endothelial cell culture and different concentrations of DHEA to the experimental architecture, and analyzed the adherence of monocyte-like cell line U937 to HUVECs. We determined the contents of nitric oxide （NO） and monoeyte chemoat-tractant protein （ MCP-1 ） in the conditioned medium of HUVECs （EC-CM） and the expression of intercellular adhesion molecule-1 （ ICAM-1 ）, and measured the levels of vascular cell adhesion molecule-1 （VCAM-1） and E-selectin of HUVECs. We used EC-CM to act on U937 cells and detected the expressions of CCR2, LFA-1 and VLA-4 mRNA in them by RT-PCR. Results DHEA significantly pro- moted NO synthesis, suppressed MCP-1 secretion in endothelial cells and decreased ICAM-1 and VCAM-1 expressions in HUVECs. The EC-CM treated with DHEA obviously inhibited the expressions of CCR2, LFA-1 and VLA-4 mRNA in U937 cells. Conclusion Dehydroepiandrosterone appears to have a protective effect on vein endothelial cells, probably by inhibiting the secretion of MCP-1, downregulating the expressions of ICAM-1 and VCAM-1, and suppressing the recruitment and adherence of monocytes to the endothelial cells.

关 键 词：脱氢表雄酮 内皮细胞 趋化因子 细胞黏附分子 

分 类 号：Q513.5[生物学—生物化学]