NO在非诺贝特抗血管紧张素Ⅳ所致心肌肥大中的作用  

Nitric oxide involves in the effects of fenofibrate on cardiomyocyte hypertrophy induced by angiotensin Ⅳ

作　　者：陈加飞[1] 王全华[1] 承欧梅[2] 吴芹[3] 蒋青松[1] 

机构地区：[1]重庆医科大学药理学教研室 [2]重庆医科大学附属第一医院神经内科,重庆400016 [3]遵义医学院药理学教研室,贵州遵义563003

出　　处：《中国药理学通报》2010年第12期1644-1648,共5页Chinese Pharmacological Bulletin

基　　金：重庆市自然科学基金计划项目(NoCSTC;2010BB5108)

摘　　要：目的研究非诺贝特(fenofibrate,FF)抗血管紧张Ⅳ(angiotensinⅣ,AngⅣ)所致心肌细胞肥大作用及其机制。方法利用乳鼠心肌细胞培养,以细胞表面积、蛋白含量和心房利钠因子mRNA表达为肥大指标,观察FF对AngⅣ诱导心肌肥大的作用。Real-time PCR和Western blot方法检测mRNA及蛋白水平的表达;比色法和硝酸还原法分别检测一氧化氮合酶(nitric oxide synthase,NOS)活性和一氧化氮(ni-tric oxide,NO)浓度。结果 AngⅣ诱导心肌细胞肥大(P<0.01);FF浓度依赖性地抑制AngⅣ的作用(P<0.01);FF0.3μmol.L-1明显上调AngⅣ导致的过氧化物酶体增殖物激活受体-α(peroxisome proliferator-activated receptor-α,PPAR-α)以及内皮型NOS mRNA和蛋白表达的降低(P<0.01),同时增加NOS活性和NO浓度(P<0.01)。PPAR-α阻断剂MK886可完全取消FF的上述作用(P<0.05)。L-精氨酸的作用与FF相似(P<0.01),NOS阻断剂NG-硝基-L-精氨酸-甲酯可完全取消其作用(P<0.01)。结论 FF可能通过激活其特异性受体PPAR-α,上调NOS表达,促进NO释放,最终产生抗AngⅣ诱导心肌肥大的作用。Aim To investigate the role of fenofibrate（FF）in cardiac hypertrophy induced by angiotensin Ⅳ（Ang Ⅳ）and its mechanisms.Methods The cultured neonatal rat cardiomyocytes were used to observe the effects of FF on cardiomyocyte hypertrophy induced by Ang Ⅳ at 1 nmol·L^-1,and the cardiomyocyte hypertrophic responses were assayed by measuring the cell surface area,protein content,and atrial natriuretic factor mRNA expression.The expressions of mRNA and protein were assayed by Real-time PCR and Western blot,respectively.Nitric oxide synthase（NOS）activity and NO concentration were determined by spectrophotometry and nitrate reduction method,respectively.Results In cultured cardiomyocytes,FF（from 0.1 to 1 μmol·L^-1could inhibit the cardiomyocyte hypertrophy induced by Ang Ⅳ at 1 nmol·L^-1 in a concentration-dependent manner（P〈0.01）.FF at 0.3 μmol·L^-1significantly increased both mRNA and protein expressions of peroxisome proliferator-activated receptor-α（PPAR-α）and endothelial NOS（eNOS）（P〈0.01）.At the same time,FF at 0.3 μmol·L^-1could also elevate NOS activity and NO concentration in cultured media（P〈0.01）.All of these effects of FF could be abolished by MK886,a selective PPAR-α antagonist（P〈0.05）.L-arginine（L-arg）at 100 μmol·L^-1acted similarly as FF olid（P〈0.01）,the effects of which could be blocked by NG-nitro-L-arginine-methyl ester,a selective NOS inhibitor（P〈0.01）.Conclusions FF attenuates cardiomyocyte hypertrophy induced by Ang Ⅳ,and the underlying mechanism may involve the elevation of the expression of PPAR-α,and the increase of the expression of eNOS,and then the release of NO.

关 键 词：血管紧张素Ⅳ 非诺贝特 过氧化物酶体增殖物激活受体-Α 一氧化氮 一氧化氮合酶 心肌肥大 

分 类 号：R-332[医药卫生] R322.11