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目的建立大鼠心肌缺血-再灌注损伤模型,通过蛋白质组学的方法研究辛伐他汀对大鼠缺血-再灌注损伤心肌线粒体代谢的保护作用。方法将大鼠随机分为辛伐他汀干预组(n=14)和生理盐水对照组(n=14),建立缺血-再灌注损伤模型,通过伊文思蓝和TTC染色评估梗死面积,提取大鼠左心室心肌线粒体蛋白行双向凝胶电泳,应用质谱分析鉴定差异蛋白点。结果辛伐他汀组和对照组相比,梗死区与危险区(梗死区+缺血区)的比值有统计学差异(29.4%±8.4%vs57.7%±6.5%,P<0.0001);梗死面积与左室面积的比值有统计学差异(15.9%±5.6%vs29.0%±8.9%,P=0.012)。双向凝胶电泳图谱分析有19个蛋白点的表达有差异,质谱鉴定了9种差异蛋白,相比对照组,辛伐他汀组4个蛋白表达上调:三功能酶亚基α(线粒体前体)、电子转移黄素蛋白脱氢酶、肌动蛋白α(心肌)、细胞色素c氧化酶亚基5A亚单位(线粒体前体);5个蛋白表达下调:L-乳酸脱氢酶B链、异柠檬酸脱氢酶[NAD]α亚基(线粒体前体)、α晶状体蛋白B链、内膜蛋白(线粒体)、肌动蛋白类似物(细胞质)。结论辛伐他汀组大鼠心肌在缺血-再灌注损伤后,心肌梗死面积显著减少,辛伐他汀改变线粒体呼吸链、能量代谢等途径上的蛋白,为阐明辛伐他汀保护缺血再灌注损伤提供了理论依据。
Objective To establish a rat model of myocardial ischemia-reperfusion injury and study the protective effect of simvastatin on myocardial mitochondrial metabolism after ischemia-reperfusion injury in rats by proteomics. Methods The rats were randomly divided into simvastatin intervention group (n = 14) and saline control group (n = 14). The model of ischemia-reperfusion injury was established. The area of infarction was assessed by Evans blue and TTC staining. The left ventricular myocardium mitochondrial protein was analyzed by two-dimensional gel electrophoresis, and the differential protein spots were identified by mass spectrometry. Results Compared with the control group, the ratio of infarction area to risk area (infarct area + ischemic area) in simvastatin group was statistically significant (29.4% ± 8.4% vs 57.7% ± 6.5%, P <0.0001) There was a statistically significant difference between the area and left ventricular area (15.9% ± 5.6% vs 29.0% ± 8.9%, P = 0.012). Nineteen protein spots were differentially expressed by two-dimensional gel electrophoresis. Nine different proteins were identified by mass spectrometry. Compared with the control group, four proteins were up-regulated in the simvastatin group: trifunctional enzyme subunit α (mitochondrial precursor) , Electron transfer flavoprotein dehydrogenase, actin α (myocardium), cytochrome c oxidase subunit 5A subunit (mitochondrial precursor); 5 protein expression down: L-lactate dehydrogenase B chain, different Citrate dehydrogenase [NAD] alpha subunit (mitochondrial precursor), alpha crystallin B chain, inner membrane protein (mitochondria), actin analogs (cytoplasm). Conclusion Simvastatin can significantly reduce myocardial infarction area after myocardial ischemia / reperfusion injury in simvastatin group. Simvastatin can alter mitochondrial respiratory chain, energy metabolism and other pathways. To elucidate the protective effects of Simvastatin on ischemia / reperfusion injury Provided a theoretical basis.