血管紧张素-(1-7)对氧化低密度脂蛋白诱导人血管内皮细胞纤溶功能异常的调节

摘要/Abstract

摘要： 目的探讨血管紧张素-(1-7)[Ang-(1-7)]对氧化低密度脂蛋白(ox-LDL)诱导血管内皮细胞分泌组织型纤溶酶原激活物(t-PA)及其抑制物-1(PAI-1)的影响。方法用酶消化法收集并培养人脐静脉内皮细胞(HUVECs),分别以不同终浓度的Ang-(1-7)(10、100、1000nmol/L)和ox-LDL[25、50、100mg/L(蛋白质含量)]进行单独或联合刺激,并以A-779(终浓度为100nmol/L)进行干预,孵育24h。以ELISA方法检测培养基上清液中t-PA和PAI-1蛋白含量,RT-PCR法检测PAI-1和t-PAmRNA的表达。结果 ox-LDL使PAI-1的分泌量显著增加,t-PA分泌显著降低,PAI-1mRNA表达升高,t-PAmRNA表达降低(P<0.001~0.05),并呈剂量依赖性;Ang-(1-7)使PAI-1分泌量及PAI-1mRNA表达显著降低,亦呈剂量依赖性(P<0.01~0.05),而对t-PA分泌及t-PAmRNA表达无影响;在混合刺激组中,与ox-LDL组比较,Ang-(1-7)使PAI-1及PAI-1mRNA表达降低、t-PA及t-PAmRNA表达升高(P<0.01~0.05),但PAI-1及PAI-1mRNA表达仍高于对照组,t-PA及t-PAmRNA表达仍低于对照组(P<0.05)。加入A-779后,Ang-(1-7)的作用消失。结论 Ang-(1-7)对氧化低密度脂蛋白诱导的血管内皮细胞纤溶异常具有显著的调节作用,此作用是通过特异性受体介导的。

Abstract: Objective To study the effect of angiotensin-(1-7)[Ang-(1-7)]on fibrinolytic imbalance induced by oxidized low-density lipoprotein (ox-LDL) in cultured human umbilical vein endothelial cells (HUVECs). Method Cultured HUVECs were incubated for 24 h in the presence of Ang-(1-7), ox-LDL and A-779 at different concentrations either separately or in combination. The final concentrations of Ang-(1-7) were 10, 100 and 1 000 nmol/L, and those of ox-LDL were 25, 50 and 100 mg protein/L. The final concentration of A-779, an Ang-(1-7) receptor antagonist, was 100 nmol/L. Tissue plasminogen activator (t-PA) and its inhibitor-1(PAI-1) antigen in the medium were determined by enzyme-linked immunosorbent assay (ELISA) and their mRNA levels by reverse transcriptional (RT) PCR. Results Ox-LDL (25-100 mg protein/L) dose-dependently increased PAI-1 release and up-regulated PAI-1 gene transcription, but decreased t-PA release and down-regulated t-PA gene transcription (P<0.001-0.05). Ang-(1-7) (100-1 000 nmol/L) dose-dependently decreased PAI-1 release and PAI-1 gene transcription (P<0.01-0.05) but had no effect on t-PA release and gene transcription. In the presence of ox-LDL, Ang-(1-7) lowered the increased levels of PAI-1 and PAI-1 mRNA, and elevated the levels of decreased t-PA and t-PA mRNA in the cells (P<0.01-0.05). The effects of Ang-(1-7) could be blocked by A-779. Conclusion Angiotensin-(1-7) effectively modulates the fibrinolytic imbalance induced by ox-LDL via its specific receptor.

中图分类号:

R394.2

王立军, 马虹, 蔡乙明, 何建桂, 廖新学, 曾武涛, 王礼春, 柳俊. 血管紧张素-(1-7)对氧化低密度脂蛋白诱导人血管内皮细胞纤溶功能异常的调节[J]. 南方医科大学学报, 2005, 25(06): 633-637.

WANG Li-jun, MA Hong, CAI Yi-ming, HE Jian-gui, LIAO Xin-xue, ZENG Wu-tao, WANG Li-chun, LIU Jun. Angiotensin-(1-7) modulates fibrinolytic imbalance induced by oxidized low-density lipoprotein in cultured human umbilical vein endothelial cells[J]. Journal of Southern Medical University, 2005, 25(06): 633-637.

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