附子、美西律、依那普利合用对L-NNA所致高血压小鼠的影响

Effect of monotherapy with Fuzi,Enalapril,Mexiletine,and their Combination on NOS inhibition induced Hypertensive Mice

目的:探讨附子、美西律、依那普利合用对L-NNA所致高血压小鼠模型的影响。方法:将雄性ICR小鼠随机分为8组:正常对照组、L-NNA模型组、L-NNA+附子组、L-NNA+依那普利组、L-NNA+附子+依那普利组、L-NNA+附子+依那普利+美西律组、L-NNA+附子+美西律组、L-NNA+美西律组。采用持续10天灌胃给予L-NNA(700mg/kg·d-1)的方法造高血压小鼠模型。造模成功后,各组持续10天分别给予0.5%羧甲基纤维素钠(CMC-Na)溶液、L-NNA、L-NNA+附子水煎液、L-NNA+依那普利、L-NNA+附子水煎液+依那普利、L-NNA+附子+依那普利+美西律、L-NNA+附子+美西律、L-NNA+美西律。给药10天后,测定各组小鼠的血压,血清中NO含量,心、肝、肾匀浆中NO和MDA的含量。结果:与正常对照组相比,模型组小鼠血压明显升高,血清和心、肝、肾组织中的NO含量降低,MDA含量升高,单独给予附子和依那普利的治疗组小鼠血压及生化指标显著改善,但两种药合用后降压效果消失;而在合用附子和依那普利的基础上给予美西律,其降压和升高血清、心、肝、肾中NO的效果比附子和依那普利合用有所提高。结论:附子和依那普利合用有明显的拮抗作用,提示附子的作用机制与RAAS系统有关,美西律能减弱附子和依那普利的拮抗作用。

Objective：To study the effect of monotherapy with Fuzi, enalapril, mexiletine, and their combination on NOS inhibition induced hypertensive mice. Methods：Male ICR mice were randomly divided into 8 groups（C, M, F, Y, F＋Y, F＋Y＋M, F＋M and Mex）. These ICR mice were treated with CMC-Na, L-NNA, L-NNA＋Fuzi, L NNA＋enalapril, L-NNA＋Fuzi＋enalapril, L- NNA＋Fuzi＋ enalapril ＋ mexiletine, L-NNA ＋ Fuzi＋ mexiletine, L-NNA ＋ mexiletine. The blood pressure were observed. The contents of NO in serum, heart, liver, kidney and MDA in heart, liver, kidney were assayed after 10 days. Results：Compared with control group, the mean arterial pressure（MAP） in model group was much higher than that of control group, the content of NO in serum, heart, liver, kidney were obviously decreased, and the content of MDA in heart, liver, kidney were significantly raised. Compared with model group, the MAP of F group and Y group was remarkablely reduced, the content of NO in serum, heart, liver, kidney was raised, and the content of MDA decreased. However, when Fuzi combined with enalapril were treated, the improvement of MAP, NO and MDA was much slighter than F group and Y group. Compared with F＋Y group, the MAP and biochemical indi- cators of F＋Y--M group were improved. Conclusion：The antagonism between Fuzi and enalapril was found in this experiment, and mexiletine can reduce this antagonism action.