奈必洛尔对高血压性心脏舒张功能不全保护作用及机制研究  

Protective effect and mechanism of nebivolol on cardiac diastolic function induced by hypertension

作　　者：张正义[1] 卢昌宏[1] 蒙颖[1] 关晓丽[1] 商波[1] 余静[1] 

机构地区：[1]兰州大学第二医院心脏病医院,甘肃兰州730030

出　　处：《兰州大学学报（医学版）》2016年第4期55-61,共7页Journal of Lanzhou University（Medical Sciences）

基　　金：甘肃省自然科学基金项目(145RJZA174);甘肃省科技支撑项目(1104FKCA150);甘肃省卫生行业科研项目(GSWSKY-2014-33)

摘　　要：目的探索不同剂量奈必洛尔对自发性高血压大鼠(SHRs)心脏舒张功能发挥保护作用的机制。方法 12周龄雄性SHRs 30只,随机分为3组:对照组(安慰剂)和高、低剂量奈必洛尔干预组(n=10),同龄雄性Wistar-Kyoto(WKY)大鼠(n=10)作为正常血压组(基线正常对照),采用无创心脏彩超及有创导管法测定心脏舒张功能,应用免疫组化测定心肌beta3-肾上腺素能受体(β3-AR)、内皮源性一氧化氮合酶(e NOS)及心肌肌浆网钙泵(Serca2a)的表达,利用转化法测定e NOS的活性及ELISA法测定NO的生成量。结果 13周龄SHRs与WKYs大鼠相比存在心脏舒张功能不全,不同剂量奈必洛尔干预2周后,无创及有创心脏舒张功能指标明显改善,心肌β3-AR,e NOS表达水平明显增加,e NOS活性及NO生成量明显增加(P<0.05或P<0.01)。结论奈必洛尔能够改善SHRs大鼠舒张功能,其作用是通过兴奋心肌β3-AR,增加e NOS和SERCA2a在心肌表达,同时提高e NOS的活性,增加心肌NO生成量而产生心脏保护效应。Objective To explore the protective effects and related mechanisms of nebivolol at different doses on diastolic dysfunction in spontaneously hypertensive rats（SHRs）. Methods 12 weeks old male SHRs were randomized to 3 groups（n=10 for each group）, control group（placebo group）, high dose nebivolol group,low dose nebivolol group, and male normotensive Wistar-Kyoto rat（WKY） group with same age as baseline control group（n=10）. Cardiac function was measured by echocardiography and invasive conductance catheter analysis before and after treatment. Immunohistochemistry was used to detect the levels of myocardium endothelium-derived nitric oxide synthase（e NOS）, beta3-adrenergic receptor, Serca 2a protein expression.e NOS activity and nitric oxide production in myocardium were also detected by transformation method and ELISA respectively. Results The results showed that cardiac diastolic function of SHRs at age of 13 weeks was worse than that in age-matched WKYs. After supplementing high dose or low dose nebivolol for two weeks, the index of diastolic function measured by echocardiography and invasive conductance catheter anal-ysis were improved（P 〈 0.05 or P 〈 0.01）. The protein levels of e NOS, beta3-adrenergic receptor and Serca 2a were increased significantly after being treated by high or low nebivolol. The e NOS activity and nitric oxide production were increased significantly in high or low dose nebivolol grups compared with control group（P 〈 0.05 or P 〈 0.01）. Conclusion Nebivolol improves the cardiac diastolic function in SHRs by exciting myocardial beta 3-adrenergic receptor, increasing the expression of myocardium e NOS and Serca2 a,augmenting e NOS activity, nitric oxide production.

关 键 词：心脏舒张功能 肾上腺素能受体 一氧化氮合酶 一氧化氮 

分 类 号：R972.4[医药卫生—药品]