长期小剂量L-NAME的使用对正常心肌损害的研究

目的 探讨慢性小剂量一氧化氮合酶抑制剂对大鼠正常心脏的损害的作用。方法 将雄性SD大鼠分成两组,即N-硝基-L-精氨酸-甲基酯(L-NAME)组和对照组,实验组(15只)用小剂量L-NAME(12mg/kg)以灌胃法口饲, 对照组(10只)予以等体积的自来水,6周后杀死动物,观察大鼠左心室/心脏总重量和心脏重量/体重的数值变化,血清NO含量,大鼠心肌中内皮型一氧化氮合酶(eNOS)的阳性表达情况及心肌的形态学和组织学变化。结果 实验组心脏重量指数和左心室重量指数较对照组分别增加8％和8.1％,血清NO含量明显下降,心肌细胞横截面面积和平均直径较对照组分别增加83.8％和35.6％,心脏动脉壁腔比率和血管周纤维化程度较对照组分别升高;≤100μm的微动脉为20％和22.77％,100～300μm之间的小冠状动脉为19.96％和29.83％。另外,L-NAME组还可观察到心肌细胞肥大,变性和坏死,炎性细胞浸润等病理变化。结论 长期小剂量L—NAME的使用会引起的冠状动脉重修复和心肌细胞肥大、心肌纤维化。其结果与大中剂量所致结果相似。

Experimental study of L-NAME Induced Mycardial Injury in Rats

Objective To study the effect of induced myocardial injury under prolonged administration with low-dosage L-NAME. Methods Myocardial injury was induced in 15 rats by L -NAME 12mg/kg dissolved in drinking water feed via mouth and compared with top water (n=10) in double blind method. The total heart mass index (HW/BW),left ventricular mass:total heart mass ra-tio(LV/HW),the level of serum N0,the endothelial nitric oxide synthase (eNOS)assay by immunohisto-chemical method,the histological and morphorogical changes of myocardium by image analyser were determined after 6 weeks. Results The experiment showed,after chronic L-NAME administration,HW/ BW and LM/HW were decreased 8.0% and 8.1% respectively(P<0.05),the serum level of NO was decreased significantly (P<0.01),diameter of myocyte were increased 83.3% and 35.6% respectively (P< 0.010). In the small srterioles,lumen diameter: vascular wall ratio and perivascular fibrosis were also increased (P<0.05) In staining slices,myocardial hy-pertrophy,de naturation,necrosis and infiltration of inflamed cells were also observed. Conclusion Low-dosage L-NAME could induced myocardial in-jury,fibrosis and coronary micro vascular remodeling.