诱导型一氧化氮合酶对大鼠心肌梗死后心室重构的影响

Effect of inducible nitric oxide synthase on ventricular remodeling in rats after myocardial infarction

目的:应用诱导型一氧化氮合酶特异性阻滞剂氨基胍阻滞急性心肌梗死后大鼠诱导型一氧化氮合酶的表达,分析其诱发的大量一氧化氮在心肌梗死后心室重构中的作用。方法:实验于2002-07/2003-05在郑州大学医学院药理实验室完成。选择Wistar大鼠60只,随机分为3组,即盐酸氨基胍组、急性心肌梗死模型组及空白对照组,每组20只。①盐酸氨基胍组,即急性心肌梗死模型大鼠(异丙肾上腺素剂量为80mg/kg,腹腔注射)应用氨基胍600mg/(kg·d)腹腔注射。②急性心肌梗死模型组,即急性心肌梗死模型大鼠用同等容量的生理盐水腹腔注射。③空白对照组,即正常大鼠腹腔注射同等容量(10mL/kg)生理盐水。各组给药时间均为4周。给药结束后,采用硝酸还原法测定血清一氧化氮、结构型一氧化氮合酶以及诱导型一氧化氮合酶的表达情况;记录左心室内压及左心室压力最大上升、下降速率等血液动力学指标;测定组织学指标包括左心室/体质量比及心肌细胞直径。结果:60只大鼠全部进入结果分析,无脱失。①急性心肌梗死模型组大鼠诱导型一氧化氮合酶及一氧化氮表达水平显著高于盐酸氨基胍组和空白对照组(F=56.231,32.560,P<0.01)。②急性心肌梗死模型组大鼠的左心室/体质量比值显著高于盐酸氨基胍组、空白对照组[(2.62±0.035,2.42±0.038,2.42±0.039)mg/g(F=47.842,P<0.01)]。急性心肌梗死模型组大鼠的心肌细胞直径显著大于盐酸氨基胍组、空白对照组[(10.54±0.56,7.41±0.33,7.26±0.37)μm(F=31.140,P<0.01)]。结论:诱导型一氧化氮合酶在急性心肌梗死后高表达及诱发大量一氧化氮促进心室重构的发生。

AIM： To inhibit the expression of inducible nitric oxide synthase （iNOS） in. rats after acute myocardial infarction by using aminoguanidine, sp, ecific iNOS parelyzer, so as to investigate the effect of nitric oxide induced by iNOS on ventricular remodeling after acute myocardial infarction. METHODS： The experiment was conducted in the Laboratory of Pharmacology, Medical College of Zhengzhou University between July 2002 and May 2003. A total of 60 Wistar rats were randomly divided into three groups： aminoguanidine group, acute myocardial infarction model group and blank control group with 20 rats in each group. ①The rats of acute myocardial infarction model （intraperitoneal injection with isoproterenol 80 mg/kg） were injected intraperitoneally with aminoguanidine 600 mg/kg per day to establish the aminoguanidine group. ② The rats of acute myocardial infarction model were injected intraperitoneally with the same volume of saline to establish the acute myocardial infarction model group. ③ The normal rats were injected intraperitoneallly with the same volume saline （10 mL/kg）. After 4 weeks of administration to three groups, the expressions of nitric oxide, constitutive nitric oxide synthase and iNOS of all rats were measured by nitric acid deoxidezation method; the left ventricular pressure, the maximum left ventricular pressure increase and decrease rate （±dp/dt max） and other hemodynamic indexes were recorded, the histological indexes including the left ventricular mass/body mass ratio, and diameters of myocardial cells were determined. RESULTS： All the 60 rats were involved in the result analysis without drop out. ①The expressions of nitric oxide and iNOS in model group were significandy higher compared with the aminoguanidine group and blank group （F=56.231, 32.560, P 〈 0.01）. ②The left ventricular mass/body mass ratio in the model group was obviously higher than those in the aminoguanidine group and blank group [（2.62±0.035）, （2.42±0.038）, （2.42±0.039） mg/g, F=47.842, P 〈 0.01], and the diameters of myocardial cells in the model group was significantly larger compared with the other two groups [（10.54±0.56）, （7.41±0.33）, （7.26±0.37） μm, F=31.140, P〈 0.01]. CONCLUSION： High expression of iNOS and nitric oxide after acute myocardial infarction can improve ventricular remodeling.