期刊文献+

Neuregulin-1β对压力超负荷心肌肥大大鼠治疗作用及机制的研究 被引量:6

Therapeutic effect of neuregulin-1β on pressure overload-induced myocardial hypertrophy in rats
下载PDF
导出
摘要 目的:研究神经调节蛋白1β(NRG-1β)对压力超负荷所致大鼠心肌肥大的治疗作用并探讨其机制。方法:Wistar雄性大鼠采用腹主动脉缩窄的方法复制心肌肥大模型。术后8周,将模型动物随机分成模型(model)组、NRG-1β治疗组(尾静脉注射NRG-1β,10μg.kg-1.d-1)和NRG-1β+赫赛汀(Herceptin,HERCE)治疗组(尾静脉注射NRG-1β的同时给予注射HERCE 10μg.kg-1.d-1)。假手术(sham)组除不以银夹缩窄腹主动脉外,其余操作同腹主动脉缩窄组。7 d后分别采用心动超声、血流动力学评价心功能;Masson染色观察心肌组织的超微结构;放射免疫法检测心肌组织中血管紧张素II(Ang II),酶联免疫吸附法测定心肌组织中肿瘤坏死因子α(TNF-α)的变化;RT-PCR法检测心肌中bcl-2和bax mRMA表达的改变。结果:(1)心动超声显示,和模型组比较,NRG-1β组左室射血分数(LVEF)及短轴缩短率(LVFS)升高,左室收缩末内径(LVESD)及舒张末内径(LVEDD)减小(P<0.01)。(2)血流动力学检测显示,NRG-1β治疗组左室收缩末压(LVESP)和左室内压最大上升和下降速率(±dp/dtmax)均明显高于模型组(P<0.01);左室舒张末压(LVEDP)低于模型组(P<0.01)。(3)与模型组比较,NRG-1β组心肌胶原容积分数(CVF)下降,心肌中Ang II和TNF-α明显减少,bcl-2 mRNA表达显著升高,而baxmRNA表达下降(P<0.01)。(4)NRG-1β+HERCE治疗组与模型组相比各项指标无明显改变(P>0.05)。结论:NRG-1可以减少压力超负荷大鼠心肌Ang II和TNF-α的生成,从而减轻Ang II和TNF-α介导的心肌间质重构;NRG-1可通过上调bcl-2 mRNA表达、下调bax mRNA表达,抑制心肌细胞的凋亡,改善压力超负荷大鼠的心功能,进而在心肌肥大的过程中发挥作用。 AIM: To investigate the therapeutic effect and the mechanism of neuregulin-1β (NRG-1β) on the rat model of myocardial hypertrophy induced by pressure overload. METHODS: Eight weeks after coarctation of abdominal aorta, the Wistar rats were randomly divided into 4 groups: myocardial hypertrophy (model) group, sham operation (sham) group, NRG-1β treatment group (intravenous injection of NRG-I[3 at dose of 10 p,g/kg daily for 7 d) and NRG- 113 + Hereeptin (HERCE) treatment group [ intravenous injection of NRG-I[3 ( 10 p^g/kg) plus HERCE ( 10 p,g/kg) daily for 7 d ]. The characteristics of heart functions were evaluated by the methods of hemodynamics and echocardiography. Masson staining was employed to observe the pathological changes of myocardial tissues. The concentration of angiotensin II (Ang II) in myocardial tissues was measured by radioimmunoassay. The level of tumor necrosis factor a (TNF-ct) in myo- cardial tissues was detected by ELISA. The mRNA expression of B-cell lymphoma/leukemia-2 (bcl-2) and bcl-2-associat- ed X protein (bax) in the myocardium was determined by RT-PCR. RESULTS: The left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LYFS) were higher, while the left ventricular end-systolic diameter (LVESD) and left ventricular end-diastolic diameter (LVEDD) were smaller in NRG-1β group than those in model group. The left ventricular end-systolic pressure (LVESP) and maximal rate of increase/decrease in left ventricular pressure ( + dp/dtmas ) were higher, and left ventricular end-diastolic pressure (LVEDP) was significantly lower in NRG-1β group than those in model group. Compared with model group, treatment with NRG-1β decreased collagen volume fraction (CVF), re-duced the Ang II and TNF-{x, increased bcl-2 mRNA expression, and decreased bax mRNA expression in myocardial tis- sues. No difference of the above parameters between model group and NRG-1 β + HERCE treatment group was observed. CONCLUSION: NRG-1 reduces the expression of Ang II and TNF-ot in myocardial tissues in pressure-overload rats, thus reducing Ang II and TNF-ot mediated myocardial interstitial remodeling. Increase in the mRNA expression of bcl-2 and de- crease in the mRNA expression of bax by NRG-1 inhibit myocardial cell apoptosis, which is responsible for its role of im- proving cardiac function of myocardial hypertrophy induced by pressure overload.
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2013年第4期609-614,共6页 Chinese Journal of Pathophysiology
关键词 神经调节蛋白1β 压力超负荷 心肌肥大 Neuregulin-1 β Pressure overload Myocardial hypertrophy
  • 相关文献

参考文献16

二级参考文献86

  • 1刘晓红,吕元红.线粒体脂肪酸氧化缺陷与能量代谢研究[J].中国优生与遗传杂志,2006,14(8):10-10. 被引量:3
  • 2冯兵,徐静,刘伟,杨晓,何作云,杨惠标.肥大心肌细胞缺氧复氧损伤特点及干预能量代谢的作用[J].中国病理生理杂志,2007,23(3):500-504. 被引量:4
  • 3Zhao Z Q,Corvera J S,Halkos M E,et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion comparision with ischemic preconditioning[J].Am J Physiol Heart Cire Physiol,2003,285(2):H579-88.
  • 4Hausenloy D J,Yellon D M.New directions for protecting the heart against ischarmia-reperfusion injury:targeting the reperfusion injury salvage kinase(RISK)-pathway[J].Cardiovasc Res,2004,61(3):448-60.
  • 5Wang R.Two′s company,three′s a crowd:can H2S be the third endogenous gascous transmitter[J].FASEB J,2002,16(13):1792-8.
  • 6Ji Y,Pang Q F,Zeng Y M,et al.Exogenous hydrogen sulde postconditioning protects isolated rat hearts against ischemia-reperfusion injury[J].Eur J Pharmacol,2008,587(1-3):1-7.
  • 7Hoiwitz L D,Fennessey P V,Shikes R H,et al.Marked reduction in myocardial infarct size due to prolonged infusion of an antioxidant during reperfusion[J].Circulation,1994,89(4):1792-801.
  • 8Zhao W,Zhang J,Lu Y,et al.The vasorelaxant effect of H2S as a novel endogenous gaseous KATP channel opener[J].EMBO J,2001,20(21):6008-16.
  • 9Elrod J W,Calvert J W,Morrison J,et al.Hydrogen sulfide attenuates myocardial ischemia-reperfusion injury by preservation of mitochondrial function[J].Proc Natl Acad Sci USA,2007,104(39):15560-5.
  • 10Zhu Y Z,Wang Z J,Ho P,et al.Hydrogen sulfide and its possible roles in myocardial ischemia in experimental rats[J].J Appl Physiol,2007,102(1):261-8.

共引文献61

同被引文献51

  • 1王学惠,卓小桢,倪雅娟,卢群,龚敏,王亭忠,马爱群.Neuregulin-1β对容量超负荷心衰大鼠的治疗作用[J].西安交通大学学报(医学版),2012,33(2):194-198. 被引量:6
  • 2杨彩鸾.卡托普利联合美托洛尔治疗老年慢性心力衰竭患者的近期与远期疗效[J].中国老年学杂志,2014,34(1):220-221. 被引量:46
  • 3常薇,祝卫国,陈军,陈学敏.雌性SD大鼠围产期铅染毒对仔鼠脑细胞Brn-3a表达及凋亡的影响[J].环境与健康杂志,2006,23(1):33-36. 被引量:3
  • 4蔡文杰,朱依纯.硫化氢对血管新生的作用及其机制[D].中国博士学位论文数据库,2007:1-8.
  • 5Du BTM, Newell KA, Huang XF. Perinatal phencyclidine treatment alters neuregulin 1/erbB4 expression and activation in later life [J]. Eur Neuropsychopharmacol, 2012,22 : 356-363.
  • 6Wang R,Shao F,Liu Z,et al. The Hsp90 inhibitor SNX-2112, induces apoptosis in muhidrug resistant K562/ADR cells through suppression of Akt/NF-kappaB and disruption of mitochondria-dependent pathways[ J ]. Chem Biol Interact, 2013,205 : 1-10.
  • 7Dairam A,Limson JL,Watkins GM,et al. Curcuminoids,eurcumin, and demethoxycurcumin reduce lead-induced memory deficits in male Wistar rats[ J 1. J Agric Food Chem, 2007,55 : 1039-1044.
  • 8Mahar I,Tan S, Davoli MA, et al. Subchronie peripheral neuregulin- 1 increases ventral hippocampal neurogenesis and induces antidepressant-like effects [ J ]. PLoS One, 2011,6 : e26610.
  • 9Rosier TW, Depboylu C, Arias-Carrion O, et al. Biodistribution and brain permeability of the extracellular domain of neuregulin-l-betal [ J ]. Neuropharmacology, 2011,61 : 1413-1418.
  • 10Li BS, Ma W, Jaffe H,et al. Cyclin-dependent kinase-5 is involved in neuregulin-dependent activation of phosphatidylinositol 3-kinase and Akt activity mediating neuronal survival[J]. J Biol Chem, 2003, 278 : 35702-35709.

引证文献6

二级引证文献33

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部