雷米普利拉和氯沙坦单用及联用对小鼠心肌缺血-再灌注损伤的心肌保护作用比较

摘要

目的:观察血管紧张素转换酶抑制剂(ACEI)雷米普利拉与血管紧张素Ⅱ受体拮抗药(ARB)氯沙坦单用及联用对心肌缺血.再灌注损伤模型小鼠心肌的保护作用.方法:将32只C57BL/6小鼠随机均分成4组,包括对照组(生理盐水)、氯沙坦(8mg·kg)组、雷米普利拉(50 μg·kg)组和氯沙坦+雷米普利拉(8mg·kg+50 μg·kg)组,建立心肌缺血-再灌注损伤模型,于再灌注前5 min静脉推注给药.术中监测相关指标如动脉血压、左室重量/体重(IVW/BW)、危险区域/左室重量比(AR/LV)、心率等,之后处死小鼠,对组织进行染色观察,以心肌梗死面积/危险区域(IS/AR)值作为保护心肌组织的检测指标.结果:各组小鼠动脉血压、LVW/BW、AR/LV和心率等无显著性差异;雷米普利拉和氯沙坦单用及联用组IS/AR值分别为(21.8±2.3)%、(20.8±3.2)%和(18.4±2.4)%.与对照组(39.6±2.0)%相比具有显著性差异(P<0.05),但单用组与联用组比较未见统计学差异.结论:雷米普利拉和氯沙坦均对小鼠心肌缺血.再灌注损伤具有心肌保护作用,但2药联用作用并不优于2药单用.%OBJECTIVE: To observe the protective effect of ACEI ramiprilat or ARB losartan alone and their combination against myocardium ischemia-reperfusion injury in mice. METHODS: 32 C57BL/6 mice were randomly divided into four groups including control group (normal saline), losartan group (8 mg·kg-1), ramiprilat group (50 μg·kg-1) and losartan+ramiprilat (8 mg·kg-1+50 μg· kg-1) group. Myocardium ischemia-reperfusion injury model was established by intravenous push for 5 min before reperfusion. Physiological index were monitored during the process, such as arterial pressure, LVW/BW, AR/LV and heart rate. Mice were sacrificed and brain tissue was observed by staining using IS/AR as index. RESULTS: There were no significant differences in arterial pressure, LVW/BW, AR/LV and heart rate. IS/AR of ramiprilat or losartan alone and their combination were (21.8 ±2.3)％, (20.8 ± 3.2)％ and (18.4 ± 2.4)％, respectively, which is significant different from (39.6 ± 2.0)％ of control group (P＜0.05). There was no significant difference between single therapy group and combination therapy group. CONCLUSION: Ramiprilat and losartan have protective effect against myocardium ischemia-reperfusion injury. But combination therapy is not prior to single therapy.