螺内酯对扩张型心肌病大鼠神经内分泌的影响

Influence of spironolactone on neuroendocrine of SD rats with dilated cardiomyopathy

目的:研究醛固酮受体拮抗剂螺内酯对扩张型心肌病神经内分泌的影响,探讨其治疗扩张型心肌病的可能机制。方法:体质量为(300±50)g的雄性SD大鼠,腹腔注射多柔比星2mg/kg(每周1次、共8周)建立扩张型心肌病心衰模型,随机分为4组(n=10):模型组、螺内酯干预Ⅰ组、螺内酯干预Ⅱ组、螺内酯干预Ⅲ组,模型组采用生理盐水10ml/(kg.d)灌胃,螺内酯Ⅰ组、Ⅱ组、Ⅲ组分别灌胃10、20、40mg/(kg.d)螺内酯,连续给药8周,于给药后第9周检测血浆、心肌中血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)水平,并检测血浆一氧化氮(NO)、血清Ⅲ型前胶原氨端肽(PⅢNP)及血浆心钠素(ANP)水平。结果:给予螺内酯干预8周后Ⅱ组、Ⅲ组血浆、心肌中AngⅡ水平下降(P<0.05)、ALD水平上升(P<0.05)、血浆NO水平上升(P<0.05)、PⅢNP水平下降(P<0.05)、ANP水平下降(P<0.05)。结论:予扩张型心肌病心力衰竭大鼠以螺内酯20mg/(kg.d)及40mg/(kg.d)治疗8周可一定程度纠正神经内分泌紊乱。

Objective：To study the effect of spironolactone,an aldosterone receptor antagonist（ARA）,on neuroendocrine of SD rats with dilated cardiomyopathy,so as to investigate its mechanism in treatment of dilated cardiomyopathy.Methods：Male SD rats,weighting（300±50） g,were intraperitoneally injected with adriamycin（2 mg/kg） once a week for 8 weeks to induce dilated cardiomyopathy models.The rat models were randomly divided into 4 groups：control group,low dose spironolactone group（10 mg/[kg·d],i.g.],middle dose spironolactone group （20 mg/[kg·d],i. g. ） and high dose spironolactone group （40 mg/[kg·d], i. g. ）. Rats in the normal control group received normal saline （10 mg/[kg·d], i. g. ）. Spironolaetone was given for 8 weeks. Angiotensin Ⅱ （Ang Ⅱ） and aldosterone （ALD） levels in the plasma and cardiac muscle homogenate were determined 9 weeks later. The plasma nitrogen monoside （NO）, N-terminal popeptide of collagen type Ⅲ （PⅢ NP） in serum and atrial natriuretic peptide （ANP） in the plasma were also measured. Results; Eight weeks after treatment,the Ang Ⅱ levels in the plasma of animals in the middle dose group and high dose group were significantly decreased（P〈0.05） ,the levels of ALD were elevated（P〈0. 05） ,those of PⅢ NP and ANP were decreased（all P〈0. 05）. Conclusion： Spironolactone at 20 mg/（kg·d） or 40 mg/（kg·d） for 8 weeks can correct the disorder in neuroendocrine system to some extents.