摘要
目的 探讨缺血前预处理对心脏缺血后再灌注损伤的影响与机制.方法 健康清洁级雄性SD大鼠66只,均建立缺血再灌注(I/R)型,然后分为3个实验组,每组22只大鼠,具体为(1)对照(control)组:心脏持续缓冲液灌注;(2) I/R组:心脏接受30 min全心缺血后行120 min再灌注;(3)阿托伐他汀处理(Ator)组:全心缺血前给予Ator 1 μmol/L灌流30 min后行I/R处理.观察与测定3组的心肌超微结构、心梗面积、血流动力学、血清乳酸脱氢酶含量、三磷酸腺苷(ATP)与烟酰胺腺嘌呤二核苷酸(NAD+)水平.结果 I/R组与Ator组结扎前降支后心电图ST段弓背向上抬高,与T波融合;control组手术前后心电图无明显变化;与I/R组比较,Ator组的心肌梗死面积显著减少(P<0.05).显微结构显示3组中心肌细胞水肿、肌原纤维排列、线粒体结构与糖原颗粒都有明显不同.L/R后,I/R组与Ator组左室收缩压(LVSP)、左室压力下降的峰速度(dp/dtmin)和心率(HR)值明显降低,而左室舒张末期压(LVEDP)明显升高(P<0.05);Ator组中上述值LVSP与dp/dtmin值明显高于I/R组,而LVEDP与HR值明显低于I/R组(P<0.05).control组的乳酸脱氢酶(LDH)水平为(164.32±20.84) U/L,I/R组为(3589.63±133.25) U/L,Ator组为(1703.25±155.80) U/L,I/R组较control组LDH水平显著增加(P<0.05);而与I/R组比较,Ator组的LDH活性显著下降(P<0.05).与control组比较,I/R组内心肌ATP与NAD+含量明显降低(P<0.05);Ator组较I/R组心肌内ATP与NAD+含量显著升高(P<0.05).结论 阿托伐他汀预处理,在I/R损伤中能有效发挥保护心肌作用,其机制是通过线粒体ATP敏感性钾通道活化与降低心肌中LDH释放介导的.
Objective To investigate the effects of pretreatment with atorvastatin (Ator) on the heart ischemia-reperfusion injury (IRI) and the possible mechanism.Methods After establishment of IRI models,66 healthy male SD rats were divided into three experimental groups (n =22 each).In control group,the rats were given cardiac perfusion continuous buffer.In IRI group,myocardia of rats accepted 30 min global ischemia and 120 min reperfusion.In Ator group,the rats were given 1 μmol/L Ator befor ischemia,and perfused for 30 min,followed by IRI.The myocardial ultrastructure,infarct size,hemodynamic,serum lactate dehydrogenase levels,adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD +) levels in three groups were observed.Results In IRI group and Ator group,arched upward ST segment elevation and T wave fusion after the anterior descending artery ligation were seen.The electrocardiogram (ECG) in the control group had no significant change after surgery.As compared with the IRI group,the myocardial infarction area in the Ator group was significantly decreased (P 〈 0.05).Microstructure showed that there was significant difference in the cardiomyocytes edema,myofibril,mitochondrial structure and glycogen granules among the three groups.After ischemia-reperfusion,the left ventricular systolic pressure (LVSP),peak velocity of left ventricular pressure drop (dp/dtmin) and heart rate (HR) values in the IRI group were decreased significantly,and the left ventricle end-diastolic pressure (LVEDP) values increased significantly (P 〈 0.05) as compared wiht the Ator group (P 〈 0.05).The lactate dehydrogenase (LDH) levels in the control group,IRI group and Ator group were (164.32 ± 20.84),(3589.63 ± 133.25) and (1703.25 ± 155.80) U/L respectively.The LDH levels in the IRI group were lower than in the control group,and those in IRI group were higher than in the Ator group (P 〈 0.05).The myocardial ATP and NAD + levels in the IRI group
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2014年第11期2498-2501,共4页
Chinese Journal of Experimental Surgery
基金
湖北省自然科学基金资助项目(2012FKB02004)
关键词
缺血前预处理
缺血后再灌注损伤
阿托伐他汀
心肌保护
Ischemic preconditioning
Ischemia reperfusion injury
Atorvastatin
Myocardial protection