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心肌去乙酰化酶SIRT3对缺血/再灌注小鼠心律失常的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2014年第3期
页码:
254-258，264
栏目:
基础研究
出版日期:
2014-03-20

文章信息/Info

Title:
Effect of cardiac deacetylase SIRT3 on ischemia-reperfusion arrhythmias in mice heart
作者:
姚 莉1; 王洪涛1; 刘 军2; 殷 玥3; 卜 艳4; 马 恒3; 郑强荪1
(第四军医大学：1.唐都医院心脏内科，
2.唐都医院老年病科，陕西 西安 710038，
3.基础医学院生理学教研室，陕西 西安 710032；
4.兰州军区临潼疗养院检验病理科，陕西 西安710600)
Author(s):
YAO Li1;  WANG Hong tao1;  LIU Jun2;  YIN Yue3;  PU Yan4;  MA Heng3;  ZHENG Qiang sun1
(1.Department of Cardiology,
2.Department of Geriatrics, Tangdu Hospital, Xi’an 710038, Shaanxi, China,
3.Department of Physiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China;
4.Department of Pathology, Lintong Sanatorium of Lanzhou Military Area Command, Xi’an 710600, Shaanxi, China)
关键词:
SIRT3; 缺血/再灌注; 心律失常; 氧化应激
Keywords:
SIRT3;  ischemia reperfusion;  arrhythmia;  oxidative stress
分类号:
R541.7
DOI:
-
文献标识码:
A
摘要:
目的:探讨心肌线粒体去乙酰化酶SIRT3对急性缺血再灌注(I/R)所致心律失常的影响。方法:以24只SIRT3基因敲除型小鼠为实验对象，用24只野生型小鼠为对照，两种小鼠均随机各分为对照组、假手术组、I/R模型组及I/R+烟酰胺腺嘌呤二核苷酸（NAD+）治疗组，每组6只小鼠(n=6)。采用冠脉左前降支结扎缺血30 min再灌注2 h建立在体大鼠急性心肌I/R模型，于术中监测心电指标。取心肌组织检测SIRT3、锰超氧化物歧化酶（MnSOD）和过氧化氢酶（Catalase）蛋白的表达和心肌内氧自由基(ROS)的水平。结果:与野生型对照小鼠相比，SIRT3基因敲除型小鼠心肌中SIRT3、MnSOD和Catalase蛋白表达的水平显著降低。心律失常评分的结果显示，SIRT3基因敲除型小鼠的假手术组即可观察到心律失常。SIRT3基因敲除可导致小鼠心肌I/R所致心律失常显著加重（与野生型模型组相比，P<0.05）。心肌I/R后，SIRT3基因敲除型小鼠心肌中ROS的增加程度明显高于野生型模型组小鼠（P<0.05）。预先采用NAD+治疗，可显著提高野生型I/R小鼠心肌SIRT3的活性（与野生型小鼠模型组相比，P<0.05），显著增加心肌MnSOD的活性，进而有效地抑制I/R小鼠心肌中ROS的水平，有效缓解I/R所致心律失常（与野生型小鼠模型组相比，均P<0.05）。但是，SIRT3基因敲除后，NAD+治疗引起的上述心肌保护作用基本消失。结论:心肌中SIRT3表达的降低可能是加重心肌I/R过程中氧化应激损伤并促发心律失常的重要机制。SIRT3正常活性的维持有助于对抗心肌I/R损伤(MIRI)的发生。
Abstract:
AIM:To investigate the role of cardiac deacetylase SIRT3 in ischemia/reperfusion (IR)-induced arrhythmias. METHODS: Twenty-four Sirt3 knockout (SIRT3 KO) mice and 24 wild-type (WT) mice were randomized into control group (Control, n=6), sham group (Sham, n=6), ischemia reperfusion group (I/R, n=6) and NAD+ treated I/R group (I/R+NAD, n=6). Wild-type and knockout mice were subjected to I (30 min)/R (2 h) and ECG was examined during I/R. NAD+ treatment was performed by intraperitoneal injection (7 days, 1 mg/kg/day) before I/R. At the end of the reperfusion period, arrhythmia score, reactive oxygen species (ROS) production, cardiac SIRT3 and Mn SOD levels were measured and analyzed. RESULTS: Compared with those in WT mice, cardiac SIRT3, Mn SOD and catalase expression decreased in SIRT3 KO mice. Arrhythmia was detected in SIRT3 KO mice under sham treatment. I/R triggered serious arrhythmia in WT mice and aggravated arrhythmia in SIRT3 KO mice (P<0.05). SIRT3 KO mice showed increased ROS production after I/R compared with WTI/R mice (P<0.05). NAD treatment significantly increased cardiac SIRT3 and MnSOD activity, inhibited ROS production and consequently suppressed I/R-induced arrhythmia in WT mice. However, NAD+ induced cardioprotctive effects were blunted in SIRT3 KO mice. CONCLUSION: Impairment of SIRT3 expression with subsequent ROS production plays an important role during I/R-induced arrhythmia and protection of SIRT3 activity may help prevent I/R-induced arrhythmia.

参考文献/References

[1]Yellon DM,Baxter GF.A“second window of protection”or delayed preconditioning phenomenon:future horizons for myocardial protection?[J].J Mol Cell Cardiol,1995,27(4):1023-1034.
[2]Dhalla NS,Elmoselhi AB,Hata T,et al.Status of myocardial antioxidants in ischemia-reperfusion injury[J].Cardiovasc Res,2000,47(3):446-456.
[3]Neckar J,Borchert GH,Hlouskova P,et al.Brief Daily Episode of Normoxia Inhibits Cardioprotection Conferred by Chronic Continuous Hypoxia.Role of Oxidative Stress and BKCa Channels[J].Curr Pharm Des,2013,19(39):6880-6889.
[4]Matejikova J,Kucharska J,Pinterova M,et al.Protection against ischemia-induced ventricular arrhythmias and myocardial dysfunction conferred by preconditioning in the rat heart:involvement of mitochondrial K(ATP)channels and reactive oxygen species[J].Physiol Res,2009,58(1):9-19.
[5]Giralt A,Villarroya F.SIRT3,a pivotal actor in mitochondrial functions: metabolism,cell death and aging[J].Biochem J,2012,444(1):1-10.
[6]Ozden O,Park SH, Kim HS,et al.Acetylation of MnSOD directs enzymatic activity responding to cellular nutrient status or oxidative stress[J].Aging (Albany NY),2011,3(2):102-107.
[7]Sundaresan NR,Gupta M,Kim G,et al.Sirt3 blocks the cardiac hypertrophic response by augmenting Foxo3a-dependent antioxidant defense mechanisms in mice[J].J Clin Invest,2009,119(9):2758-2771.
[8]Pillai VB,Sundaresan NR,Jeevanandam V,et al.Mitochondrial SIRT3 and heart disease[J].Cardiovasc Res,2010,88(2):250-256.
[9]Fryer RM,Hsu AK,Nagase H,et al.Opioid-induced cardioprotection against myocardial infarction and arrhythmias:mitochondrial versus sarcolemmal ATP-sensitive potassium channels[J].J Phar-macol Exp Ther,2000,294(2):451-457.
[10]Xue L,Xu F,Meng L,et al.Acetylation-dependent regulation of mitochondrial ALDH2 activation by SIRT3 mediates acute ethanol-induced eNOS activation[J]. FEBS Lett,2012,586(2):137-142.
[11]Sack MN,Emerging characterization of the role of SIRT3-mediated mitochondrial protein deacetylation in the heart[J].Am J Physiol Heart Circ Physiol,2011,301(6):H2191-H2197.
[12]Marrotte EJ,Chen DD,Hakim JS,et al.Manganese superoxide dismutase expression in endothelial progenitor cells accelerates wound healing in diabetic mice[J].J Clin Invest,2010,120(12):4207-4219.
[13]Sack MN.The role of SIRT3 in mitochondrial homeostasis and cardiac adaptation to hypertrophy and aging[J].J Mol Cell Cardiol, 2012,52(3):520-525.
[14]Jing E, Emanuelli B, Hirschey MD, et al. Sirtuin-3 (Sirt3) regulates skeletal muscle metabolism and insulin signaling via altered mitochondrial oxidation and reactive oxygen species production[J].Proc Natl Acad Sci U S A,2011.108(35):14608-14613.

备注/Memo

备注/Memo:
收稿日期：2013-06-27.
基金项目：国家自然科学基金项目资助（81170108）
通讯作者：郑强荪，教授，主要从事心脏组织工程及复杂心律失常射频消融治疗 Email：qiangsunzheng@gmail.com
共同通讯作者：马恒，副教授，主要从事心肌内源性保护机制研究 Email:hengma@fmmu.edu.cn
作者简介：姚莉，主治医师，硕士生 Email：yaolifsmyk2009@sina.com
更新日期/Last Update: 2014-03-21