吴茱萸次碱抗Ang Ⅱ诱导的心肌细胞肥大作用以及对NO的影响
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摘要
目的观察吴茱萸次碱(Rut)对血管紧张素Ⅱ(AngⅡ)所致乳鼠心肌细胞肥大的影响及一氧化氮(NO)的作用。方法利用乳鼠心肌细胞原代培养,以细胞直径、蛋白含量(BCA法)、心房利钠因子(ANF)mRNA表达为心肌肥大指标,利用试剂盒检测上清液中NO含量和一氧化氮合酶(NOS)活性。Real time RT-PCR检测心肌细胞内皮型一氧化氮合酶(eNOS)和ANF mRNA的表达。结果 AngⅡ(1.0μmol/L)使心肌细胞直径明显增大,蛋白含量明显增加,ANF mRNA表达明显增加(P<0.05);同时,eNOS mRNA表达减少,心肌细胞上清液NOS活性和NO含量明显降低(P<0.05)。Rut (0.1、1.0、10μmol/L)剂量依赖性地减轻AngⅡ诱导的心肌肥大(P<0.05)。Rut上调eNOS mRNA表达,使NOS活性和NO含量明显增加(P<0.05)。结论 Rut可抑制AngⅡ诱导的心肌细胞肥大,该作用可能与其促进NO释放有关。
Objective To investigate the effects of rutaecarpine on cardiomyocyte hypertrophy induced by angiotensin Ⅱ(Ang Ⅱ) and its possible influence on nitric oxide(NO).Methods The cardiomyocyte hypertrophy was characterized in rat primary cardiomyocytes by the cell diameter,protein content(BCA method),atrial natriuretic factor(ANF) mRNA expression,and the histological change.The mRNA expressions of endothelial NO synthase(eNOS) and ANF were detected by real time PCR.The enzymatic activity of NOS and the concentration of NO were measured by using commercial kits.Results Ang Ⅱ significantly induced cardiomyocyte hypertrophy,which the cell diameter,protein level and ANF mRNA were increased,and hypertrophic morphology changes were also appeared.Meanwhile,Ang Ⅱ decreased the expression of eNOS mRNA,which occurred in parallel with declining NOS activity and NO concentration(P<0.05).The effect of Ang Ⅱ was inhibited by rutaecarpine(0.1,1.0,10 μmol/L) in dose-dependently manner(P<0.05).Conclusion Rut can ameliorate Ang II-induced cardiomyocyte hypertrophy in vitro,which may be related to the release of NO.
Objective To investigate the effects of rutaecarpine on cardiomyocyte hypertrophy induced by angiotensin Ⅱ(Ang Ⅱ) and its possible influence on nitric oxide(NO).Methods The cardiomyocyte hypertrophy was characterized in rat primary cardiomyocytes by the cell diameter,protein content(BCA method),atrial natriuretic factor(ANF) mRNA expression,and the histological change.The mRNA expressions of endothelial NO synthase(eNOS) and ANF were detected by real time PCR.The enzymatic activity of NOS and the concentration of NO were measured by using commercial kits.Results Ang Ⅱ significantly induced cardiomyocyte hypertrophy,which the cell diameter,protein level and ANF mRNA were increased,and hypertrophic morphology changes were also appeared.Meanwhile,Ang Ⅱ decreased the expression of eNOS mRNA,which occurred in parallel with declining NOS activity and NO concentration(P<0.05).The effect of Ang Ⅱ was inhibited by rutaecarpine(0.1,1.0,10 μmol/L) in dose-dependently manner(P<0.05).Conclusion Rut can ameliorate Ang II-induced cardiomyocyte hypertrophy in vitro,which may be related to the release of NO.
引文
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[11]林淑娴,任丽娜,孙安盛.吴茱萸碱、吴茱萸次碱和吴茱萸总碱的小鼠急性毒性[J].遵义医学院学报,2015,38(2):57-60.
[12]侯化化,张婧怡,孙安盛,等.吴茱萸碱抑制血管紧张素Ⅱ致大鼠血管平滑肌细胞增殖的研究[J].华西药学杂志,2014,29(6):645-647.
[2] 林晶晶,王静,沈涛.吴茱萸生物碱类对心血管的药理作用研究进展[J].中国临床研究,2015,28(10):1392-1396.
[3] Li W Q,Li X H,Du J,et al.Rutaecarpine attenuates hypoxia-induced right ventricular remodeling in rats[J].Naunyn Schmiedebergs Arch Pharmacol,2016,389(7):757-767.
[4] 陈洪,黄波,吴芹,等.吴茱萸次碱改善压力超负荷所致大鼠左心结构及功能异常(英文)[J].遵义医学院学报,2018,41(2):119-125.
[5] 彭晓凤,陈加飞,蒋青松,等.PI3K/Akt-NO信号通路在Ang Ⅳ诱导大鼠心肌肥大中的作用[J].重庆医学,2012,41(11):1055-1061.
[6] Xu Y,Chen X P,Zhang F,et al.Rutaecarpine inhibits intimal hyperplasia in a balloon-injured rat artery model [J].Chin J Integr Med,2018,24(6):429-435.
[7] 肖坤,谢东明.心肌肥厚的发病机制与治疗现状[J].赣南医学院学报,2017,37(3):495-500.
[8] 陈小文,黄燮南,吴芹.人参皂苷Rb1抑制Ang Ⅱ诱导的心肌细胞肥大[J].遵义医学院学报,2008,31(5):457-460.
[9] 符佳佳,刘培庆.一氧化氮在心肌肥大中的作用及机制[J].中国动脉硬化杂志,2006,5(14):451-454.
[10]邱模昌,彭维杰.吴茱萸次碱药理作用研究进展[J].科技信息,2012(1):651- 652.
[11]林淑娴,任丽娜,孙安盛.吴茱萸碱、吴茱萸次碱和吴茱萸总碱的小鼠急性毒性[J].遵义医学院学报,2015,38(2):57-60.
[12]侯化化,张婧怡,孙安盛,等.吴茱萸碱抑制血管紧张素Ⅱ致大鼠血管平滑肌细胞增殖的研究[J].华西药学杂志,2014,29(6):645-647.