雷米普利对心肌梗死后心衰大鼠非梗死区胶原的抑制作用

目的 研究心肌梗死后心衰大鼠非梗死区心肌血管紧张素Ⅱ(Ang Ⅱ)及其Ⅰ型受体(AT1-R)表达对心室重构的影响及雷米普利的干预作用.方法 结扎大鼠左冠状动脉前降支并饲养6 w的16只存活大鼠,随机分为模型组及雷米普利组,每组8只,另取8只大鼠为假手术组,连续灌胃给药4 w后测定大鼠血流动力学参数,ELISA方法检测血清及左心室非梗死区AngⅡ的含量,RT-PCR 法测定左心室非梗死区心肌组织AT1-R mRNA表达水平,Masson染色观察非梗死区心肌胶原的沉积.结果 雷米普利能明显升高左心室内压最大上升和最大下降速率(±dp/dt_(max)),降低左心室收缩压(LVSP)、左心室舒张末压(LVEDP)(P<0.05或P<0.01),但对心率(HR)、收缩压(SBP)、舒张压(DBP)无明显影响(P>0.05),同时明显降低血清及左心室非梗死区AngⅡ的含量及下调AT1-R mRNA 表达水平(P<0.01或P<0.001),Masson染色可见非梗死区心肌胶原沉积明显减轻.结论 雷米普利对梗死后心衰大鼠非梗死区心肌间质胶原重构有显著的抑制作用,其作用机制与下调AT1-R表达水平及减轻胶原沉积有关.

Inhibiting effect of Ramipril on collagen in heart failure rats after AMI in noninfarction zone

Objective To investigate the effects of Ramipril on the content of angiotensin Ⅱand the expression of AT1-R mRNA in heart failure rats after acute myocardial infarction (AMI) in noninfarction zone(NIZ).Methods The rat models of heart failure were established by left anterior descending coronary artery deligation. After 6 w, 24 surviving rats were divided into sham,model and Ramipril groups at random,8 rats in each,and were treated with medicines by intragastric administration respectively. At 10 w, left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure(LVSP), +dp/dtmax and-dp/ dtmaxof left ventricular pressure were measured. In addition, the contents of Ang Ⅱ in serum and in non-infarction zone were quantified with ELISA, the expression of AT1-R mRNA was detected by RT-PCR in NIZ. Furthermore, myocardial pathological changes were observed by light microscope after Masson dyeing. Results Ramipril decreased significantly LVSP and LVEDP, the contents of AngⅡ in serum and in non-infarction zone, downregulated AT1-R mRNA expression in NIZ(P<0.05～0.01),whereas increased ±dp/dtmax(P<0.05～0.01), lightened collagen deposition in NIZ with Masson dyeing, but no influence on HR, SBP and DBP(P>0.05). Conclusions Ramipril inhibit myocardial interstitial collagen reconstitution on heart failure after AMI, which may be related to downregulating AT1-R mRNA expression and lightening collagen deposition in NIZ in the development heart failure.