我们的网站为什么显示成这样？

可能因为您的浏览器不支持样式，您可以更新您的浏览器到最新版本，以获取对此功能的支持，访问下面的网站，获取关于浏览器的信息：

|本期目录/Table of Contents|

SIRT3对SD大鼠体外循环心功能的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2016年第4期
页码:
419-423
栏目:
基础研究
出版日期:
2016-04-01

文章信息/Info

Title:
Effect of SIRT3 on cardiac functions in Sprague Dawley rats undergoing cardiopulmonary bypass
作者:
王志法1; 2; 陈 涛2; 赵 婷3; 殷 强2; 孙国成2; 朱海龙2; 顾春虎2
( 第四军医大学：1.生理学教研室，2.西京医院心脏外科，3.西京医院麻醉科，陕西 西安 710032)
Author(s):
WANG Zhi-fa1; 2;  CHEN Tao2;  ZHAO Ting3;  YIN Qiang2;  SUN Guo-cheng2;  ZHU Hai-long2;  GU Chun-hu2
(1.Department of Physiology, School of Basic Medical Sciences；
2.Department of Cardiovascular Surgery, 3.Department of Anesthesia, Xijing Hospital；
Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
SIRT3; AMPK; Glut-4; 体外循环; 心功能
Keywords:
SIRT3;  AMPK;  Glut-4;  cardiopulmonary bypass;  cardiac function
分类号:
R54
DOI:
-
文献标识码:
A
摘要:
目的 探讨心肌线粒体去乙酰化酶 SIRT3对大鼠体外循环(CPB)所致急性心功能下降的影响及机制。方法 Sprague-Dawley(SD)成年大鼠30只，随机分为3组：对照组(sham组)、体外循环组(CPB组)、外源性烟酰胺腺嘌呤二核苷酸(NAD+)治疗体外循环组(NAD+治疗组),每组10只（n=10）。麻醉复苏后1 h，采用彩色多普勒超声诊断仪检测左心室收缩末期内径(LVIDs)、左心室舒张末期内径(LVIDd)、短轴缩短率(FS)及左心室射血分数(LVEF)。然后处死SD大鼠，取心肌组织，检测 AMPK、p-AMPK和心肌细胞膜Glut-4的蛋白表达及SIRT3和AMPK的活性。结果 与sham组相比，CPB组在CPB后血糖升高(P<0.05)，心功能下降(P<0.05)，具体表现为LVIDs和LVIDd值升高(P<0.05)、FS和LVEF值下降(P<0.05)，CPB后SD大鼠心肌的SIRT3活性下降(P<0.05)，下游的AMPK磷酸化水平及AMPK活性下降以及心肌细胞膜Glut-4的蛋白表达下降（均P<0.05）；预先采用外源性NAD+治疗，可显著降低血糖水平(P<0.05)，提高CPB后SD大鼠心肌SIRT3的活性，促进心肌AMPK的磷酸化和该酶活性的升高(均P<0.05)，并增加CPB大鼠心肌细胞膜Glut-4蛋白表达(P<0.05)；与CPB组相比，NAD+治疗组心功能降低有所改善，表现为LVIDs和LVIDd值下降、FS和LVEF值升高(均P<0.05)。结论 NAD+治疗可明显改善SD大鼠CPB后的心功能，其机制可能与激活SIRT3，进而增加下游AMPK的磷酸化和该酶活性，以及增加心肌细胞膜Glut-4蛋白表达，并促进CPB术后心肌对葡萄糖的摄取和利用以及ATP的生成有关。
Abstract:
AIM To investigate the role of cardiac deacetylase SIRT3 in cardiopulmonary bypass-induced cardiac dysfunction. METHODSThirty adult Sprague Dawley (SD) rats, aged 4-6 months and weighing 320-420 g, were randomly divided into three groups (n=10 each): sham operation group (sham group, n=10), cardiopulmonary bypass group (CPB group, n=10) and NAD+plus cardiopulmonary bypass group (NAD+treatment group, n=10). CPB model was established by cannulation between right jugular vein and tail arteries. NAD+was given by intraperitoneal injection (2 mg/kg) before CPB. Cardiac function indexes including left ventricular internal diastolic diameter (LVIDd), left ventricular internal diameter at end-systole (LVIDs), fraction shortening (FS) and left ventricular ejection fraction (LVEF) were measured by ultrasound imaging system 1 h after anesthesia resuscitation. SD rats were sacrificed to obtain myocardial specimens. Activity of SIRT3 and AMPK and levels of p-AMPK, AMPK and Glut-4 were measured and analyzed. RESULTSCompared with those in sham group, blood glucose level increased, LVIDd and LVIDs scores in CPB group were significantly higher, FS and LVEF scores were markedly lower, and levels of p-AMPK and Glut-4 and activity of SIRT3 and AMPK decreased (both P<0.05). NAD+treatment significantly decreased blood glucose, increased SIRT3 activity, AMPK activity, levels of p-AMPK, Glut-4, and consequently suppressed CPB-induced impairments of cardiac functions (both P<0.05). CONCLUSIONImpairment of SIRT3 activity with subsequent Glut-4 transfer descent plays an important role in decreased cardiac functions after CPB.

参考文献/References

[1]Nee L,Giorgi R,Garibaldi V,et al.Ischemia-modified albumin and adenosine plasma concentrations are associated with severe systemic inflammatory response syndrome after cardiopulmonary bypass[J].J Crit Care,2013,28(5):747-755.
[2]Sato H,Carvalho G,Sato T,et al.The association of preoperative glycemic control, intraoperative insulin sensitivity,and outcomes after cardiac surgery[J].J Clin Endocrinol Metab,2010,95(9):4338-4344.
[3]Zhou R,Liu J.A risk factor for hyperlactatemia after surgical repair of secundum atrial septal defect in children:What is the problem?[J].J Thorac Cardiovasc Surg,2011,141(2):598-599.
[4]Zheng R,Gu C,Wang Y,et al.Impacts of intensive insulin therapy in patients undergoing heart valve replacement[J].Heart Surg Forum,2010,13(5):E292-E298.
[5]Onyango P,Celic I,Mccaffery JM,et al.SIRT3, a human SIR2 homologue,is an NAD-dependent deacetylase localized to mitochondria[J].Proc Natl Acad Sci U S A,2002,99(21):13653-13658.
[6]Samarska IV,Henning RH,Buikema H,et al.Troubleshooting the rat model of cardiopulmonary bypass:effects of avoiding blood transfusion on long-term survival, inflammation and organ damage[J].J Pharmacol Toxicol Methods,2013,67(2):82-90.
[7]Floh AA,Manlhiot C,Redington AN,et al.Insulin resistance and inflammation are a cause of hyperglycemia after pediatric cardiopulmonary bypass surgery[J].J Thorac Cardiovasc Surg,2015,150(3):498-504.
[8]Doenst T,Wijeysundera D,Karkouti K,et al.Hyperglycemia during cardiopulmonary bypass is an independent risk factor for mortality in patients undergoing cardiac surgery[J].J Thorac Cardiovasc Surg,2005,130(4):1144.
[9]黑飞龙，房秀生.体外循环心内直视手术中胰岛素抵抗的研究[J].中华实验外科杂志,2000,17(5):437-438.
[10]Bertrand L,Ginion A,Beauloye C,et al.AMPK activation restores the stimulation of glucose uptake in an in vitro model of insulin-resistant cardiomyocytes via the activation of protein kinase B[J].Am J Physiol Heart Circ Physiol,2006,291(1):H239-H250.
[11]Ohta M,Fujinami A,Kobayashi N,et al.Two chalcones,4-hydroxyderricin and xanthoangelol,stimulate GLUT4-dependent glucose uptake through the LKB1/AMP-activated protein kinase signaling pathway in 3T3-L1 adipocytes[J]. Nutr Res,2015,35(7):618-625.
[12]Feige JN,Auwerx J.Transcriptional targets of sirtuins in the coordination of mammalian physiology[J].Curr Opin Cell Biol,2008,20(3):303-309.
[13]Pillai VB,Sundaresan NR,Kim G,et al.Exogenous NAD blocks cardiac hypertrophic response via activation of the SIRT3-LKB1-AMP-activated kinase pathway[J].J Biol Chem,2010,285(5):3133-3144.

备注/Memo

备注/Memo:
收稿日期：2015-11-13.
基金项目：
基金项目：国家自然科学基金项目资助（81370352）；陕西省科技攻关项目资助（2009K17-04）
通讯作者：顾春虎，副教授，主要从事婴幼儿心脏外科疾病研究 Email：guchunhu@fmmu.edu.cn
作者简介：王志法，硕士生 Email：1127101384@qq.com
更新日期/Last Update: 2016-04-01