一氧化氮合酶2抑制剂对大鼠心肌梗死后左心室形态及心功能的影响

Effects of NOS2 inhibitor on left ventricular morphologic and haemodynamic parameters after myocardial infarction in rats

目的 :观察选择性一氧化氮合酶 2 (NOS2 )抑制剂S -甲基硫脲 (SMT)对心肌梗死 (MI)后左心室形态学和血流动力学指标的影响 ,探讨NOS2在MI后心功能障碍形成过程中的作用。方法 :于大鼠冠状动脉结扎前 30min给予SMT灌胃 ,6周后测定左心室形态学和血流动力学指标、心肌NOS2表达量、血浆NO2 -/NO3 -水平、心肌纤维化程度。结果 :MI后 6周 ,心脏非梗死区NOS2表达量、血浆NO2 -/NO3 -水平、中心静脉压和左室舒张末压高于对照组。使用SMT可降低血浆NO2 -/NO3 -水平 [(2 6 . 6± 6. 1) μmol/Lvs (5 0 . 1± 10 .4 ) μmol/L ,P <0. 0 1],减少心肌梗死范围 (36 . 0 %± 7 .2 .vs 4 2 .6 %± 8 .6 % ,P <0 0 5 ) ,减轻心室扩张 [LVD ,(6 .6± 0 . 3)mmvs (7 .2± 0 . 3)mm ,P <0. 0 1],减小心肌细胞直径 [(15 .1± 1. 6 ) μmvs (16 . 9± 2 . 3) μm ,P <0 . 0 5 ],减轻心肌纤维化 [CVF ,4 . 1%± 1. 1%vs5 . 7%± 1 .2 % ,P <0 . 0 1],降低中心静脉压 [(0 . 9± 0 .3)mmHgvs (1. 5± 0 . 5 )mmHg ,P <0 . 0 1]和左室舒张末压 [(8 .1± 2 . 4 )mmHgvs(13. 4± 3 .1)mmHg ,P <0 . 0 1],提高存活率 (72 . 4 %vs39 .3% ,P <0 . 0 5 )。结论 :大鼠MI后 ,NOS2可能起促进心功能障碍形成的作用。

AIM: To study the role of NOS2 in the devel op ment of cardiac dysfunction after rat myocardial infarction by observing effects of S-methylisothiourea (SMT) on left ventricular morphology and haemodynamics. METHODS: An selective NOS2 inhibitor, was used. Administration o f SMT by gavage began 30 min before coronary ligation. Six weeks later, left ventricular morphologic and haemodynamic parameters were o bserved,and NOS2 expression, plasma NO 2-/NO 3- level and myocardial fibr osis were studied. RESULTS: Six weeks after myocardial infarction, NOS2 level in ra t non-infarct cardiac muscle, plasma NO 2-/NO 3- level, CVP and LVEDP were higher than that in controls. Long term administration of SMT decreased plasma NO 2-/NO 3- level [(26.6±6.1) μmol/L vs (50.1±10.4) μmol/L, P<0.01], decreased infarct size (36.0%±7.2% vs 42.6%±8.6%, P <0.05), improved ventricular dilation [LVD, (6.6±0.3) mm vs (7.2± 0.3) mm, P<0.01], reduced myocyte diameter [(15.1±1.6) μm vs (1 6.9±2.3) μm, P<0.05], improved cardiac fibrosis(CVF, 4.1%±1.1% v s 5.7%±1.2%, P<0.01), improved CVP [(0.9±0.3) mmHg vs (1.5 ±0.5) mmHg, P<0.01] and LVEDP [(8.1±2.4) mmHg vs (13.4±3.1 ) mmHg, P<0.01], and increased survival rate (72.4% vs 39.3%, P <0.05). CONCLUSIONS: NOS2 is involved in the development of cardiac dysf unction after myocardial infarction. Inhibition of NOS2 could ameliorate heart r emodeling and improve cardiac function.