肾素-血管紧张素系统对大鼠心肌缺血和缺血再灌注后左心室功能的影响

Effect of RAS on left ventricular function after myocardialischemia and reperfusion in anesthetized rats

目的 观察肾素 血管紧张素系统 (RAS)对大鼠心肌缺血和缺血再灌注后左心室功能的影响 ,以及给予氯沙坦和培哚普利干预的结果。方法 结扎大鼠左冠状动脉前降支造成心肌梗死 ,30min后松解结扎线再灌注心肌 6 0min ,假手术组只穿线不结扎 ,大鼠随机分为假手术组、生理盐水对照组、氯沙坦组、培哚普利组。监测大鼠心肌缺血 30min和缺血再灌注 6 0min时血流动力学和左心室功能、循环RAS组分、肌酸激酶 (CK)和去甲肾上腺素(NE)等指标。结果 ①与假手术组比较 ,对照组的左室舒张末压在冠脉结扎和再灌注后均升高 ,而血压、左室收缩压和±dp/dt则显著降低 ;与对照组比较 ,两个用药组大鼠的心功能明显改善 ;②对照组血浆NE、CK水平明显高于假手术组和用药组 ;③对照组血浆各RAS组分水平比假手术组明显升高 ;用药组则明显抑制RAS活性。结论 ①大鼠心肌缺血和再灌注后发生左心室功能障碍 ;②心肌缺血和缺血再灌注损伤后循环RAS被激活 ;③氯沙坦和培哚普利可以保护心肌细胞 。

Objective To investigate the effect of RAS on left ventricular function after myocardial ischemia and reperfusion in rats, and the effects of losartan and perindopril. Methods The Sprague Dawley rats were randomly assigned to one of the following treatment groups: ① sham operated group (S); ② control group (C); ③ losartan treated group (L); ④ perindopril treated group (P). Infarction was produced by left coronary artery ligation. Following 30 min of occlusion, reperfusion of the ischemic area for 60 min was allowed. The suture thread was applied but not tied in sham operated group. During ischemia and reperfusion periods, heart rate (HR), mean blood pressure (MAP), heart rate pressure product (RPP), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and ±dp/dt were measured. Plasma level of angiotensin(Ang)Ⅰ, AngⅡ, plasma renin activity(PRA),aldosterone(Ald) and the plasma concentration of CK and NE were measured. Results ① The LVEDP was higher in C and drug treatment groups than in S one, moreover, with the value of LVEDP highest in C group. The ±dp/dt was significantly reduced in C and treatment groups, with the value in C group being lowest(P<0.05). ② After drug administration, the MAP and RPP were significantly lower in L and P groups than in S and C ones (P<0.05).③ Comparing with S group, the plasma concentration of CK and NE were increased in C group. The plasma CK and NE levels were lower in L and P groups than in C group (P<0.05). ④ Comparing with S group, the plasma levels of AngⅠ, AngⅡ, PRA and Ald were higher in C group (P<0.05). Conclusions ① After myocardial ischemia and reperfusion, left ventricular dysfunction occurred. ② The circulating RAS was activated after ischemia and reperfusion. ③ Losartan and perindopril could restrict the necrosis of myocardium, inhibit the release of catecholamine, and improve left ventricular function.