孟鲁司特钠的心肌保护作用及对一氧化氮合酶的影响

目的观察白三烯受体拮抗剂孟鲁司特钠对大鼠心肌坏死的保护作用及一氧化氮合酶（NOS）的影响。方法大鼠sc异丙肾上腺素（2 mg·kg^-1）造成心肌坏死模型，ig不同剂量孟鲁司特钠，测定血清乳酸脱氢酶（LDH）、肌酸磷酸激酶（CK）、丙二醛（MDA）及心肌一氧化氮（NO）含量和坏死心肌面积，免疫组化检测心肌NOS 3种同功酶的表达。结果大鼠预先给予孟鲁司特钠10或30 mg·kg^-1可降低血清LDH，CK，MDA含量，缩小心肌坏死面积。孟鲁司特钠30 mg·kg^-1还能激活内皮型NOS（eNOS）表达，抑制诱导型NOS（iNOS）表达，促进心肌NO释放。结论孟鲁司特钠通过拮抗白三烯的致炎作用及激活eNOS、抑制iNOS表达，对大鼠异丙肾上腺素心肌坏死具有保护作用，在心肌缺血治疗中有潜在应用前景。

Cardioprotective effect and influence on NOS expression of Montelukast sodium in rats

AIM: To determine the protective effect and influence on NOS expression of Montelukast sodium--a leukotriene antagonist on myocardial necrosis in rats. METHODS: Myocardial ischemia and necrosis were induced in rats by isoproterenol (2 mg.kg-1, s.c., qd for 2 d). Serum activity of LDH, CK, MDA, NO content in myocardium and scope of myocardial necrosis were measured. nNOS, iNOS and eNOS were investigated by immunohistochemical evaluation. RESULTS: Decreased serum level of LDH, CK, MDA and attenuated myocardial necrosis area were found in rats pretreated with Montelukast sodium 10 and 30 mg.kg-1. Montelukast sodium 30 mg.kg-1 also enhanced NO content in myocardium. Montelukast sodium activated the eNOS expression and reduced the iNOS expression. CONCLUSION: Montelukast sodium is cardioprotective during myocardial injury in rats by halting the leukotrienes-induced inflammatory response and upregulating the eNOS expression as well as downregulating the iNOS expression. This may represent an approach to the treatment of myocardial ischemia with leukotriene antagonists.