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术前辛伐他汀治疗对体外循环后心肌保护的疗效及机制

Efficacy and Mechanism of Preoperative Simvastatin Therapy on Myocardial Protection after Extracorporeal Circulation.

作者信息

Hua Ping, Liu Jianyang, Tao Jun, Zou Rongjun, Lin Xifeng, Zhang Dingwen, Yang Songran

机构信息

Department of Cardiovascular Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.

Department of Vascular Surgery, Henan Provincial People's Hospital, Zhengzhou 450003, China.

出版信息

Biomed Res Int. 2017;2017:6082430. doi: 10.1155/2017/6082430. Epub 2017 Nov 8.

Abstract

BACKGROUND

Cardiopulmonary bypass (CPB) causes systemic inflammatory response and ischemia-reperfusion (IR) injury.

OBJECTIVE

To investigate the effect and mechanism of simvastatin on myocardial injury in cardiac valve surgery with CPB.

METHODS

One hundred thirty patients were randomly assigned to the statin group ( = 65) or control group ( = 65). Simvastatin was administered preoperatively and postoperatively. Duration of intensive care unit stay, duration of assisted ventilation, and left ventricular ejection fraction were recorded. Plasma was analysed for troponin T (cTnT), isoenzyme of creatine kinase (CK-MB), tumor necrosis factor alpha (TNF-), interleukin-6 (IL-6), and interleukin-8 (IL-8). Ultrastructure of the myocardium and autophagosomes were observed. Beclin-1, LC3-II/I, P62, AMPK, and the phosphorylation of AMPK in cardiomyocytes were detected.

RESULTS

Simvastatin significantly reduced the duration of assisted ventilation ( = 0.030) and ejection fraction was significantly higher in the statin group ( = 0.024). Simvastatin significantly reduced the levels of cTnT, CK-MB, TNF-, IL-6, and IL-8 ( < 0.05), reduced the expression of LC3-II/LC3-I and Beclin 1, and increased the expression of phosphorylation of AMPK. Simvastatin reduced the generation of autophagosomes and the ultrastructural injuries to myocardium.

CONCLUSION

Perioperative statin therapy reduced myocardial injury by regulating myocardial autophagy and activating the phosphorylation of AMPK. The registration number of this study is ChiCTR-TRC-14005164.

摘要

背景

体外循环(CPB)可引发全身炎症反应和缺血再灌注(IR)损伤。

目的

探讨辛伐他汀对CPB心脏瓣膜手术中心肌损伤的影响及机制。

方法

130例患者随机分为他汀组(n = 65)和对照组(n = 65)。术前及术后给予辛伐他汀。记录重症监护病房停留时间、辅助通气时间和左心室射血分数。分析血浆中的肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)、肿瘤坏死因子α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-8(IL-8)。观察心肌超微结构和自噬体。检测心肌细胞中Beclin-1、LC3-II/I、P62、AMPK及AMPK的磷酸化水平。

结果

辛伐他汀显著缩短辅助通气时间(P = 0.030),他汀组射血分数显著更高(P = 0.024)。辛伐他汀显著降低cTnT、CK-MB、TNF-α、IL-6和IL-8水平(P < 0.05),降低LC3-II/LC3-I和Beclin 1的表达,并增加AMPK磷酸化的表达。辛伐他汀减少自噬体的产生和心肌超微结构损伤。

结论

围手术期他汀治疗通过调节心肌自噬和激活AMPK磷酸化减轻心肌损伤。本研究注册号为ChiCTR-TRC-14005164。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/32d4/5698794/9275aa7daab1/BMRI2017-6082430.001.jpg

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