首页 | 本学科首页   官方微博 | 高级检索  
     

SIRT3对SD大鼠体外循环心功能的影响
引用本文:王志法,陈涛,赵婷,殷强,孙国成,朱海龙,顾春虎. SIRT3对SD大鼠体外循环心功能的影响[J]. 心脏杂志, 2016, 28(4): 419-423
作者姓名:王志法  陈涛  赵婷  殷强  孙国成  朱海龙  顾春虎
作者单位:( 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)
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)
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。

关 键 词:SIRT3   AMPK   Glut-4   体外循环   心功能
收稿时间:2015-11-13

Effect of SIRT3 on cardiac functions in Sprague Dawley rats undergoing cardiopulmonary bypass
WANG Zhi-fa;CHEN Tao;ZHAO Ting;YIN Qiang;SUN Guo-cheng;ZHU Hai-long;GU Chun-hu. Effect of SIRT3 on cardiac functions in Sprague Dawley rats undergoing cardiopulmonary bypass[J]. Chinese Heart Journal, 2016, 28(4): 419-423
Authors:WANG Zhi-fa  CHEN Tao  ZHAO Ting  YIN Qiang  SUN Guo-cheng  ZHU Hai-long  GU Chun-hu
Affiliation:WANG Zhi-fa;CHEN Tao;ZHAO Ting;YIN Qiang;SUN Guo-cheng;ZHU Hai-long;GU Chun-hu;Department of Physiology,School of Basic Medical Sciences;Fourth Military Medical University;Department of Cardiovascular Surgery;Fourth Military Medical University;Department of Anesthesia,Xijing Hospital;Fourth Military Medical University;
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.
Keywords:
本文献已被 CNKI 等数据库收录!
点击此处可从《心脏杂志》浏览原始摘要信息
点击此处可从《心脏杂志》下载免费的PDF全文
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号