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目的:探讨醛固酮受体拮抗剂螺内酯(spironolactone,安体舒通)预防一氧化氮减少致高血压心肌重塑的可行性。方法:取8周龄雄性Wistar大鼠19只,随机分成高血压大鼠实验组12只,其中又分为高血压组、预防组各6只;正常血压对照组7只。高血压大鼠实验组用L-硝基精氨酸(N-omega-nitro-L-arginine,LNNA,7.5mg/kg,腹腔注射,每日2次,共4周)诱导高血压心肌重塑大鼠12只,其中6只同时以安体舒通(20mg/kg,每日1次,灌胃,共4周)治疗。分别观察其动脉血压、左心室相对重量、丝裂素活化蛋白激酶(mitogen-activatedproteinkinase,MAPK)活性、胶原蛋白含量、亚硝酸盐浓度、心肌组织形态学改变等。结果:高血压组亚硝酸盐浓度降低,血压、MAPK活性及胶原蛋白含量均明显升高,左心室肥大,心肌细胞肥大及心肌纤维化。安体舒通可明显降低动脉压、MAPK活性,减轻左心室肥大、心肌细胞肥大及心肌纤维化。结论:安体舒通通过竞争性抑制醛固酮与其受体结合,降低MAPK活性,可防止一氧化氮生成减少所致高血压心肌重塑及血压持续升高。
OBJECTIVE: To investigate the feasibility of aldosterone receptor antagonist spironolactone (Angstromide) for prevention of myocardial remodeling induced by nitric oxide (NO) reduction. Methods: Totally 19 male Wistar rats aged 8 weeks were randomly divided into experimental group (n = 12) and hypertensive rats (n = 6). There were 6 rats in prevention group and 7 rats in normal control group. Hypertensive rats were induced hypertensive myocardium by N-omega-nitro-L-arginine (LNNA, 7.5mg / kg, intraperitoneal injection twice daily for 4 weeks) Twelve rats were treated with spironolactone (20 mg / kg once daily for 4 weeks). The arterial blood pressure, left ventricular relative weight, mitogen-activated protein kinase (MAPK) activity, collagen content, nitrite concentration and myocardial histomorphology were observed. Results: Hypertension group decreased nitrite concentration, blood pressure, MAPK activity and collagen content were significantly increased, left ventricular hypertrophy, myocardial hypertrophy and myocardial fibrosis. Spironolactone can significantly reduce arterial pressure, MAPK activity, reduce left ventricular hypertrophy, myocardial hypertrophy and myocardial fibrosis. CONCLUSIONS: Spironolactone inhibits the binding of aldosterone to its receptor and decreases the activity of MAPK, preventing the remodeling of hypertensive myocardium and the continuous increase of blood pressure caused by the decrease of nitric oxide production.