天津医药 ›› 2019, Vol. 47 ›› Issue (1): 26-31.doi: 10.11958/20180551

• 实验研究 • 上一篇    下一篇

代谢综合征合并心肌梗死大鼠模型的建立及 氧化应激相关机制的探讨

张毅 1,2#,任梦萌 3#,方涛 4,邸研博 4,崔晓旭 4,刘勇 2,贺晶 2,国欣涛 5,田凤石 2△   

  1. 基金项目:天津市卫生行业重点攻关项目(16KG146);天津市慢性病防治科技重大专项(17ZXMFSY00200);天津市第四中心医院博硕基 金项目 作者单位:1天津医科大学研究生院(邮编300070);2天津市第四中心医院心血管内科;3河北省沧州市中心医院重症医学科;4天津市第 四中心医院中心实验室,5心胸外科 #张毅和任梦萌为共同第一作者 作者简介:张毅(1979),男,硕士在读,住院医师,主要从事心血管内科方面研究;任梦萌(1990),女,硕士,住院医师,主要从事重症医学方 面研究 △通讯作者 E-mail: fengshitian080101@126.com
  • 收稿日期:2018-04-09 修回日期:2018-12-06 出版日期:2019-01-15 发布日期:2019-01-15
  • 通讯作者: 田凤石 E-mail:daixiezonghezheng@163.com
  • 基金资助:
    天津市应用基础与前沿技术研究计划基金资助项目;天津市卫生行业重点攻关项目;天津市慢性病防治科技重大专项

Establishment of OLETF rat model of metabolic syndrome with myocardial infarction and study on the mechanisms of oxidative stress

ZHANG Yi1, 2#, REN Meng-meng3#, FANG Tao4, DI Yan-bo4, CUI Xiao-xu4, LIU Yong2, He Jing2, GUO Xin-tao5, TIAN Feng-shi2△   

  1. 1 Graduate School, Tianjin Medical University, Tianjin 300070, China; 2 Department of Cardiology, Tianjin 4th Center Hospital; 3 Intensive Care Unit, Cangzhou Central Hospital; 4 Central Laboratory, 5 Cardio-Thoracic Surgery, Tianjin 4th Center Hospital △Corresponding Author E-mail: fengshitian080101@126.com
  • Received:2018-04-09 Revised:2018-12-06 Published:2019-01-15 Online:2019-01-15
  • Supported by:
    Tianjin Research Program and Application Foundation and Advanced Technology;Fund program:High-Priority Health Projects of Tianjin;Tianjin major science and technology projects

摘要: 目的 建立一种稳定、易复制、符合临床实际的代谢综合征(MS)合并心肌梗死(MI)大鼠模型,并探讨MS 对心肌梗死的影响。方法 OLETF大鼠用于建立MS模型,给予高脂饲料喂养;LETO大鼠作为对照,给予标准饲料 喂养。MS模型造模成功后,将对照大鼠和模型大鼠分别给予假手术处理(sham组,MS-Sham组)和心肌梗死造模(MI 组,MS-MI组)。心肌梗死造模采用结扎大鼠心脏左前降支方法制作心肌梗死模型,假手术处理只开胸穿线不结扎 左前降支。超声心动图测量大鼠左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室短轴缩短率 (LVFS)、左心室射血分数(LVEF)。酶联免疫吸附试验(ELISA)测定心肌组织谷胱甘肽过氧化物酶(GSH-Px)、总抗 氧化能力(T-AOC)、髓过氧化物酶(MPO)、丙二醛(MDA)水平;免疫印迹和RT-PCR法检测心肌组织硫氧还原蛋白 (TRX)和硫氧还原蛋白相互作用蛋白(TXNIP)的蛋白和 mRNA 水平。结果 MS 和 MI 对大鼠的 LVEDD、LVESD、 LVFS、LVEF均有影响(P<0.05),两者交互效应对大鼠的LVEDD、LVFS、LVEF有影响(P<0.05)。MS和MI对大鼠心 肌组织的GSH-Px、T-AOC、MPO、MDA及TRX和TXNIP蛋白和mRNA水平均有影响(P<0.05),两者交互效应对大鼠 心肌组织的T-AOC、MDA和TXNIP mRNA水平有影响(P<0.05)。结论 本研究建模方法简便、实用性强,符合MS 合并心肌梗死临床发病实际。TRX系统稳定性被破坏可能是MS加重心肌组织氧化应激水平及左室功能下降的内 源性机制之一。MS在MI中发挥影响左室功能的作用机制仍需进一步探讨。

关键词: 心肌梗死, 硫氧还蛋白质类, 疾病模型, 动物, 代谢综合征;左室功能, 氧化应激

Abstract: Objective To establish a stable, easily replicable, clinically relevant metabolic syndrome (MS) rat model of myocardial infarction, and explore the impact of MS on myocardial infarction. Methods Eighteen OLETF rats were used to establish the MS model,and 18 LETO rats were used as the control group. Rats were given high-fat diet and standard feed respectively. Model LETO rats and OLETF rats were randomly divided into sham operation group (sham group, MS-sham group) and myocardial infarction group (MI group, MS-MI group), 9 rats for each group. Echocardiography was used to measure left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular fraction shortening (LVFS), and left ventricular ejection fractions (LVEF). The levels of glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxidase (MPO) and malondialdehyde (MDA) in myocardial tissue were determined by ELISA. Western blot assay and RT-PCR were used to detect protein and mRNA levels of thioredoxin (TRX) and thioredoxin interacting protein (TXNIP) of myocardial tissue. Results There were effects of MS and MI on LVEDD, LVESD, LVFS and LVEF in rats (P<0.05). The interaction between the two groups showed effects on LVEDD, LVFS and LVEF in rats (P<0.05). MS and MI showed effects on GSH-Px, T-AOC, MPO, MDA, and levels of TRX and TXNIP protein and mRNA in rat myocardial tissues (P<0.05). The interaction between the two groups showed effects on T-AOC, MDA and mRNA levels of TXNIP in rat myocardial tissues (P<0.05). Conclusion This model is simple and practical. The disruption of TRX system stability may be one of the endogenous mechanisms, by which MS aggravates oxidative stress levels and decreases left ventricular function of myocardial tissue. The mechanism of MS affecting left ventricular function in MI still needs further investigation.

Key words: myocardial infarction, thioredoxins, disease models, animal, metabolic syndrome, left ventricular function; oxidative stress