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

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

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m RNA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。

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.