期刊文献+

Akt信号通路在紫绀型先天性心脏病患儿心肌慢性缺氧适应中的作用 被引量:1

Role of Akt signal pathway in chronically hypoxic children with cyanotic congenital heart disease
原文传递
导出
摘要 目的:探讨Akt信号通路在紫绀型先天性心脏病患儿心肌慢性缺氧适应中的意义。方法:收集紫绀型和非紫绀型先天性心脏病患儿共50例,其中紫绀型26例(紫绀组),动脉血氧饱和度(SaO2)60%~89%;非紫绀型24例(非紫绀组),SaO2>95%,均不伴肺动脉高压[肺动脉收缩压<30mmHg(1mmHg=0.133kPa)]。心脏外科手术体外循环前留取右心耳组织,应用Western blot方法检测心肌组织蛋白激酶B(总Akt)和磷酸化蛋白激酶B(Ser473P-Akt)表达水平,免疫组织化学技术检测心肌组织总Akt和Ser473 P-Akt蛋白表达部位与水平。结果:与非紫绀组相比,紫绀组患儿心肌组织Ser473P-Akt蛋白表达水平明显增高(P<0.01),而2组患儿总Akt蛋白表达水平差异无统计学意义(P>0.05)。紫绀组患儿心肌组织Ser473P-Akt蛋白大部分表达在心肌细胞的胞质,胞核亦有微弱表达,而非紫绀组心肌细胞则无明显Ser473P-Akt蛋白表达。2组患儿总Akt蛋白绝大部分也表达在心肌细胞的胞质,胞核亦有微弱表达,但表达部位和水平差异无统计学意义。紫绀组患儿心肌组织Ser473 P-Akt蛋白表达水平与患儿术前SaO2呈负相关(r=-0.771,P<0.01)。结论:Akt信号通路激活可能是紫绀型先天性心脏病患儿心肌慢性缺氧适应的重要信号调控机制之一。 Objective:To explore the effect of Akt signal pathway in chronically hypoxic children with cyanotic congenital heart disease(CHD).Method:When the cardiopulmonary bypass was not established before cardiac surgery,samples from the auricle of right atrium were collected from children who were not associated with pulmonary arterial hypertension with cyanotic(n=26,SaO2: 60%-89%) and acyanotic(n=24,SaO2〉95%) CHD.The level and site of the protein expression of Akt and Ser473P-Akt were examined by Western blot and immunohistochemistry.Result:There was no statistical difference between cyanotic and acyanotic groups in Akt protein expression(P〈0.05),however,the protein level of Ser473P-Akt in cyanotic group was significantly higher than that in acyanotic group(P〈0.01) and was negatively correlated with preoperative SaO2.Conclusion:Cyanotic hearts adapt to chronic hypoxia through activation of Akt signal pathway,which is responsible for cardioprotection in the chronically hypoxic children with cyanotic CHD.
出处 《临床心血管病杂志》 CAS CSCD 北大核心 2012年第5期373-376,共4页 Journal of Clinical Cardiology
基金 重庆市教委科研项目(No:kj100321)
关键词 先天性心脏病 慢性缺氧 蛋白激酶B(Akt) 磷酸化蛋白激酶B congenital heart disease chronic hypoxia protein kinase B(Akt) phospho-Akt(Ser473)
  • 相关文献

参考文献16

  • 1苏肇伉.先天性心脏病外科进展[J].上海第二医科大学学报,2004,24(3):153-158. 被引量:29
  • 2NAJM H K, WALLEN W J, BELANGER M P, et al. Does the degree of cyanosis affect myocardial adenosine triphosphate levels and function in children undergoing surgical procedures for congenital heart disease? [J].J Thorac Cardiovase Surg, 2000, 119: 515-524.
  • 3RAFIEE P, SHI Y, KONG X, et al. Activation of protein kinases in chronically hypoxic infant human and rabbit hearts: role in cardioprotection [J]. Circulation, 2002,106: 239- 245.
  • 4SHAO Z, BHATTACHARYA K, HSICH E, et al. C-Jun N-terminal kinases mediate reactivation of Akt and eardiomyocyte survival after hypoxic injury in vitro and vivo[J]. Cir Res,2006,98 : 111-- 118.
  • 5UCHIYAMA T, ENGELMAN R M, MAULIK N, et al. Role of Akt signaling in mitochondrial survival pathway triggered by hypoxic preconditioning [J]. Circulation, 2004,109 : 3042 - 3049.
  • 6MATSUI T, TAO J, DEL MONTE F, et al. Akt activation preserves cardiac function and prevents injury after transient cardiac ischemia in vivo[J]. Circulation, 2001,104 : 330-335.
  • 7KOLAR F, OSTADAL B. Molecular mechanisms of cardiac protection by adaptation to chronic hypoxia [J]. Physiol Res, 2004,53 (Suppl) : S3-S13.
  • 8刘晓燕,田杰,邓兵,李娅莎,张晓萍.HIF-1α在青紫型先天性心脏病患儿心脏慢性缺氧适应机制中的作用[J].临床儿科杂志,2009,27(5):410-413. 被引量:3
  • 9PERSAD S, ATTWELL S, GRAY V, et al. Regulation of protein kinase B/Akt-serine 473 phosphorylation by integrin-linked kinase: critical roles for kinase activity and amino acids arginine 211 and serine 343 [J]. J Biol Chem,2001,276:27462-27469.
  • 10RAPHAEL J, ABEDAT S, RIVO J, et al. Volatile anesthetic preconditioning attenuates myocardial apoptosis in rabbits after regional ischemia and reperfusion via Akt signaling and modulation of Bcl-2 family proteins[J]. J Pharmaeol Exp Ther, 2006, 318:186 -- 194.

二级参考文献42

  • 1徐志伟,苏肇伉,朱德明,张志芳,丁文祥.深低温低流量灌注方法在小儿四联症纠治术中的应用[J].临床儿科杂志,1996,14(3):163-164. 被引量:13
  • 2Kolar F,Ostádal B.Molecular mechanisms of cardiac protection by adaptation to chronic hypoxia[J].Physiol Res,2004,53(Suppl 1):S3-S13.
  • 3Lee JW,Bae SH,Jeong JW,et al.Hypoxia-inducible factor (HIF-1) alpha:its protein stability and biological function[J].Exp Mol Med,2004,36(1):1-12.
  • 4Semenza GL.Hydroxylation of HIF-1:oxygen sensing at the molecular level[J].Physiology,2004,19(4):176-182.
  • 5Cai Z,Manalo DJ,Wei G,et al.Hearts from rodents exposed to intermittent hypoxia or erythropoietin are protected against ischemia-reperfusion injury[J].Circulation,2003,108(1):79-85.
  • 6Lee SH,Wolf PL,Escudero R,et al.Early expression of angiogenesis factors in acute myocardial ischemia and infarction[J].N Engl J Med,2000,342(9):626-633.
  • 7Nau PN,Van Natta T,Ralphe JC,et al.Metabolic adaptation of the fetal and postnatal ovine heart:regulatory role of hypoxia-inducible factors and nuclear respiratory factor-1[J].Pediatr Res,2002,52(2):269-278.
  • 8Semenza GL.HIF-1 and human disease:one highly involved factor[J].Genes Dev,2000,14(16):1983-1991.
  • 9Safran M,Kaelin WG Jr.HIF hydroxylation and the mammalian oxygen-sensing pathway[J].J Clin Invest,2003,111(6):779-783.
  • 10Potter C J, Pedraza LG, Xu T. Akt regulates growth by directly phosphorylating Tsc2 [ J ]. Nat Cell Biol, 2002,4 (9) :658-665.

共引文献67

同被引文献2

引证文献1

二级引证文献4

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