培哚普利和螺内酯对高血压大鼠心血管重构及纤溶的影响

摘要

目的：探讨血管紧张素转换酶抑制剂培哚普利（ perindopril ）和醛固酮受体拮抗剂螺内酯（ spironlactone ）对实验性高血压大鼠心脏、血管重构的逆转作用及纤溶系统的影响。方法腹主动脉缩窄法建立高血压动物模型，44只雄性Wistar 大鼠随机分为高血压模型组、培哚普利组（2 mg · kg-1· d-1，螺内酯组（20 mg· kg-1· d-1）和假手术组对照组。治疗12周后，各组分别应用超声检测心脏结构和功能，主动脉内径，壁厚，病理检测主动脉形态，测定纤溶酶原激活物抑制物-1（plasminogen activator inhibitor-1， PAI-1），组织纤溶酶原激活剂（tissure plasminogen activator，t-PA）。结果心脏超声结果显示，螺内酯组和培哚普利组同高血压模型组比较，舒张末期室间隔厚度，左心室后壁厚度，相对室壁厚度，左心室质量，左心室内径，左心房内径明显下降（ P ＜0殮．05或＜0．01）；胸主动脉壁厚明显下降（ P ＜0．01），病理检测胸主动脉内中膜厚度，胸主动脉内中膜厚度/内径明显下降（ P ＜0．01）。血浆PAI-1水平培哚普利组，螺内酯组同假手术组比较明显升高（ P ＜0．01），2组同高血压组比较差异无统计学意义（ P ＞0．05）。 t-PA 4组差异无统计学意义（ P ＞0．05）。结论高血压导致心脏、血管重构，纤溶活性降低，培哚普利和螺内酯均能逆转心脏和血管重构，但对高血压导致的低纤溶状态未产生明显逆转作用。%Objective To investigate the effects of perindopril and spironolactone on cardiovascular remodeling and fibrinolysis system in experimental hypertensive rats .Methods The models of hypertensive rat were established by using the method of abdominal aortic coarctation .The 44 male Wistar rats were randomly divided into 4 groups:hypertension model group , perindopril group ( hypertensive rats subjected to perindopril , 2mg· kg-1· d-1),spironolactone group (hypertensive rats receiving spironolactone,20mg· kg-1 · d-1), sham-operation group ( control group ) ,with 11 rats in each group .After 12-week treatment ,the cardiac and aortic structure and function of the rats were examined by ultrasonography ,meanwhile,aortic morphous was observed ,and the levels of plasma tissue plasminogen activator ( t-PA ) and plasminogen activator inhibitor ( PAI-1 ) were detected.Results As compared with those in hypertension model group , interventricular septal thickness (IVSTd),left ventricular posterior wall thickness (LVPWTd),relative wall thickness (RWT) of left ventricular, left ventricular mass ( LVM) ,left ventricular end-diastolic diameter ( LVEDD) ,left atrial diameter ( LVD) and the thickness of aorta in perindopril group and spironolactone group were significantly decreased ( P <0.01 or P <0.05);the media thickness of aorta , the ratio of media thickness to diameter of lumen aorta were obviously decreased ( P <0.01 ).The plasma levels of PAI-1 in perindopril group and spironolactone group were significantly increased,as compared with those in control group ( P <0.01),however,there were no significant differences in plasma levels of PAI-1 between the two drug groups and hypertension model group ( P >0.05). There were no significant differences in t-PA levels among the four groups ( P >0.05 ).Conclusion Hypertension can resulte in cardiovascular remodeling and hypofibrinolysis ,both perindopril and spironolactone can reverse cardiovascular remodeling ,however ,they do not have obvious reverse effect on fribrinolysis .