瑞舒伐他汀后处理联合缺血后处理减轻2型糖尿病大鼠心肌缺血再灌注损伤  

Rosuvastatin enhances the protective effects of ischemic postconditioning on myocardial ischaemia-reperfusion injury in type 2 diabetic rat

作　　者：蔡炜[1] 方军[1] 陈昭阳[1] 林运灵[1] 吴黎明[1] 陈良龙[1] 

机构地区：[1]福建医科大学附属协和医院心内科福建省冠心病研究所,福州350001

出　　处：《中华心血管病杂志》2010年第9期814-818,共5页Chinese Journal of Cardiology

摘　　要：目的 探讨瑞舒伐他汀后处理联合缺血后处理对2型糖尿病大鼠心肌缺血再灌注损伤的影响.方法 取健康、雄性、清洁级Wistar大鼠80只,体重180～220 g.链脲佐菌素联合尼克酰胺建立2型糖尿病大鼠模型,选取成模大鼠随机分成6组（各组10只）,分别为：假手术组、对照组、瑞舒伐他汀后处理组（RSV组）、缺血后处理组（Post组）、瑞舒伐他汀后处理＋缺血后处理组（RSV＋Post组）、瑞舒伐他汀后处理＋缺血后处理＋LY294002组[RSV＋Post＋LY294002组,于再灌注前15 min经颈外静脉给予磷酸肌醇3激酶（PI3K）抑制剂LY294002],均予心肌缺血30 min,再灌注120min处理.TTC染色测定心肌梗死面积、电镜观察心肌细胞超微结构变化、Western blot测定心肌组织磷酸化内皮型一氧化氮合酶（eNOS）蛋白（p-eNOS）及总eNOS蛋白（t-eNOS）的表达.结果 RSV＋Post组eNOS磷酸化水平显著高于对照组（0.332±0.013比0.079±0.004,P〈0.01）,心肌线粒体超微结构损伤显著轻于对照组（1.15±0.32比3.51±0.32,P〈0.01）,心肌梗死面积显著小于对照组[（33±2）%比（75±2）%,P〈0.01].结论 瑞舒伐他汀后处理联合缺血后处理可能通过激活PI3K/AKT/eNOS信号通路,减轻2型糖尿病大鼠心肌缺血再灌注损伤.Objective To investigate the combined effect of rosuvastatin （RSV） and ischemic postconditioning （PC） on myocardial ischemia-reperfusion （I/R） injury in a type 2 diabetic rat model. Methods Type 2 diabetic （ induced by streptozotocin plus nicotinamide） rats, undergoing 30 min ischemia and 120 min reperfusion, were divided into six groups （n = 10 each）： Sham, I/R without other interventions, RSV before reperfusion, PC with 3 cycles of 10 s reperfusion and 10 s ischemia, RSV ＋ PC and RSV ＋ PC ＋ PI3-K inhibitor LY294002. Myocardial infarct size （IS）, ultrastructural change and myocardial expression of phosphorylated eNOS/total eNOS were determined. Results IS and ultrastructural damages were all significantly reduced and myocardial eNOS phosphorylation was significantly increased in RSV and PC groups compared with the L/R group （all P 〈 0. 05 ） these benefical effects were further enhanced by RSV ＋ PC （ all P 〈 0. 05 vs. RSV and PC, respectively）. The beneficial effects were significantly attenuated by PI3K inhibitor LY294002. Conclusions The results indicate that RSV ＋ PC could alleviate myocardial ischemia-reperfusion injury in this type 2 diabetic model by activating PI3K/AKT/eNOS signaling pathway.

关 键 词：心肌再灌注损伤 糖尿病 2型 瑞舒伐他汀 

分 类 号：R965[医药卫生—药理学] R587.2[医药卫生—药学]