中文摘要：

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（rt=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。SIR13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，SIR73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。

英文摘要：

AIM： To investigate the role of cardiac deacetylase SIRT3 in ischemia/reperfusion （I/R）-in duced 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 MnSOD 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 arrhvthmia.