摘要
目的 研究血管紧张素Ⅱ(AngⅡ)和血管紧张素转换酶抑制剂(ACEI),卡托普利和AngⅡ1型受体(AT-1)拮抗剂缬沙坦对人脐静脉内皮细胞(HUVECs)1型纤溶酶原激活物抑制剂(PAH)、组织型纤溶酶原激活剂(tPA)蛋白的释放及活性的影响。方法 将不同浓度的AngⅡ(10^-6~10^-9mol/L)与HUVECs共同孵育24h,以及将10^-6mol/L的AngⅡ与HUVECs作用不同时间(0、4、8、12、24h)后,用细胞酶联免疫法和发色底物法分别检测细胞培养液中PAI-1、tPA的含量及活性,并观察卡托普利和缬沙坦干预后的影响。结果 10^-6mol/LAngⅡ作用HUVECs 24h后,可使细胞分泌的PAI-1含量与对照组相比明显增高(280±15.60 vs 83.33±10.56)ng/mL,P〈0.01),PAI-1活性明显增加(9.25±0.39 vs 7.53±0.33)Iu/mL,P〈0.01),AngⅡ虽也可刺激tPA含量增加(101.67±3.78 vs 70±5.62)ng/mL,(P〈0.01),但PAI-1的增量是tPA增量的6~7倍(Δ196.67±21.34 vs Δ31±6.50)ng/mL,(P〈0.01),AngⅡ对tPA活性无影响(0.97±0.05 vs 0.95±0.08)ng/mL,(P〉0.05);缬沙坦可显著抑制AngⅡ的促PAI-1分泌作用(212.67±5.38 vs 290±6.57)IU/mL,(P〈0.01),而卡托普利对Ang1/的促PAI-1分泌作用无明显抑制作用(278.33Ⅱ9.16 vs 290±6.57)IU/mL,(P〉0.05)。结论 AngⅡ可促使HUVECs分泌PAI-1,并使其活性增加;AngⅡ亦可刺激tPA分泌,但作用弱于PAI-1,对其活性无明显影响。缬沙坦可抑制AngⅡ促HUVECs分泌PAI-1的作用;卡托普利的作用不显著。
Objective To observe the effects of angiotensin Ⅱ (Ang Ⅱ }, angiotensin converting enzyrne inhibitor (ACEI) captopril, and a specific type 1 angiotensin Ⅱ receptor (AT-1) antagonist valsartan on plasminogen activator inhibitor-1 (PAI-1) and tissue type plasminogen activator (tPA) in cultured human umbilical vein endothelial cells (HUVECs). Methods Cultured HUVECs were incubated with Ang Ⅱ of 10^-6-10^-0mol/L for 24 hours. Captopril and valsartan were added respectively to the culture medium with or without Ang Ⅱ. Antigens and activities of PAI-land tPA in the cultured medium were measured by enzyme linked immunosorbent assay (ELISA) and the indirect chromogenic assay. Results Compared to control, 10^-9-10^6mol/L AngⅡ markedly increases PAI-1 antigen ( 280 ±15. 60 vs 83.33±10.56)ng/mL, ( P〈0. 05) and activities (9.25±0. 39 vs 7. 53±0.33 )IU/mL, ( P〈0. 01, ) in a dose dependent and time dependent manner while no changes in tPA activities were found. Valsartan inhibited the increase of PAI-1 induced by Ang Ⅱ (212.67±5.38 vs 290±6.57)ng/mL, (P〈0.01) . Conclusion Ang Ⅱ stimulated the release of PAI-1 and tPA, but the increments of PAI-1 were much more than those of tPA. The activities of tPA were not increased by Ang Ⅱ. Valsartan inhibited the effects of Ang Hinduced release of PAI-1. Our findings suggest that Ang Ⅱ enhanced thrombosis by decreasing fibrinolytic activity.
出处
《高血压杂志》
CSCD
北大核心
2005年第10期637-641,共5页
Chinese Journal of Hypertension
基金
山西省2000年回国留学人员科研资助项目