Objective: To determine whether administiation of captopril, an ACE inhibitor, can induce unique gene expression in hearts from spontaneously hypertensive rats (SHR). Methods: Differential screening was used to isolat...Objective: To determine whether administiation of captopril, an ACE inhibitor, can induce unique gene expression in hearts from spontaneously hypertensive rats (SHR). Methods: Differential screening was used to isolate captopril response genes through a human fetal cDNA library, and reverse northern blot technique was applied to analyze gene expression. Results: Administration of captopril in SHR significantly lowered blood pressure, heart rate (HR), and the ratio of heart to body weight was compared with untreated SHR. Three captopril responsive cDNA sequences (expreed sequence tags, ESTs) were identified. One ESTs were highly homologous to human mitochondria gene and other 2 were novel and unknown genes. Conclusion: The benefit of captopril may be mediated, at least in part, by having an effect on the expression of a specific gene involved in cardiac remodeling and function in essential hypertension.展开更多
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...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。展开更多
基金National Natural Sciences Foundation of China!No.39725013National Natural Sciences Foundation of China!No.39770341
文摘Objective: To determine whether administiation of captopril, an ACE inhibitor, can induce unique gene expression in hearts from spontaneously hypertensive rats (SHR). Methods: Differential screening was used to isolate captopril response genes through a human fetal cDNA library, and reverse northern blot technique was applied to analyze gene expression. Results: Administration of captopril in SHR significantly lowered blood pressure, heart rate (HR), and the ratio of heart to body weight was compared with untreated SHR. Three captopril responsive cDNA sequences (expreed sequence tags, ESTs) were identified. One ESTs were highly homologous to human mitochondria gene and other 2 were novel and unknown genes. Conclusion: The benefit of captopril may be mediated, at least in part, by having an effect on the expression of a specific gene involved in cardiac remodeling and function in essential hypertension.
文摘目的 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。
