白黎芦醇减轻Ⅱ型糖尿病小鼠心肌缺血/再灌注损伤的作用  

Role of resveratrol in attenuating myocardial ischemia/reperfusion injury in type Ⅱ diabetic mice

作　　者：杨强[1] 王海昌[1] 高超[1] 冯世栋[1] 孙璐[1] 刘毅[1] 陶凌[1] 

机构地区：[1]第四军医大学西京医院心血管内科,陕西西安710032

出　　处：《心脏杂志》2012年第3期292-297,共6页Chinese Heart Journal

基　　金：国家高技术研究发展计划项目资助(2009AA02Z104);国家重大新药创制计划项目资助(2009ZX09103-673);国家自然科学基金面上项目资助(81170186)

摘　　要：目的:探讨白黎芦醇(RSV)减轻Ⅱ型糖尿病(T2DM)小鼠心肌缺血/再灌注损伤(MI/RI)的作用及其机制。方法:采用喂养高脂饮食结合小剂量链脲佐菌素(STZ)建立T2DM小鼠模型。造模成功后立即给予RSV(10 mg/kg)每日1次灌胃,连续3周。实验分为正常假手术组、正常手术对照组、DM假手术组、DM手术对照组、RSV组、CpC组,每组20只。手术方式采用心脏冠状动脉左前降支结扎30 min、再灌注3 h或24 h。抑制剂组于术前1 h腹腔注射Compound C(20 mg/kg)。用TTC染色法检测心肌梗死(MI)面积,TUNEL法检测心肌细胞凋亡,ELISA法检测caspase-3活性、血浆脂联素(APN)水平,Western blot法检测AMPK、p-AMPK及脂肪组织APN的含量。结果:喂养高脂饮食结合小剂量STZ能够成功建立T2DM小鼠模型。与DM手术对照组相比,RSV饲喂能够减轻T2DM小鼠MI/RI,减小MI面积、减少心肌细胞凋亡(P<0.01),降低caspase-3的活性(P<0.05)。RSV还能够上调脂肪组织APN表达,逆转T2DM小鼠低APN血症(P<0.01)。AMPK抑制剂Compound C可显著减弱RSV的心肌保护作用(P<0.05)。结论:RSV可通过逆转T2DM小鼠的低脂联素血症,在MI/RI时发挥对心肌的保护作用。T2DM was induced by a high-fat diet （HD） plus low-dose i.p. streptozotocin （STZ） injection. Mice were treated with 10 mg/kg RSV daily by intragastric administration for 3 weeks after acknowledgement of T2DM. Mice were divided into six groups： sham group, I/R group, T2DM sham group, T2DM ＋ I/R group, RSV group, and CpC group. After 30 rain ischemia by slip-knot ligature of the left anterior descending coronary artery, myocardium was reperfused for 3 h after knot release （for apoptosis by TUNEL, caspase-3 activity by ELISA） or 24 h （for infarct size determination by TYC staining）. At 1 h before MI/RI, com- pound C （an AMPK inhibitor） was administered i.p. （20 mg/kg）. RESULTS： HD feeding plus low- dose STZ injection successfully induced T2DM. RSV alleviated MI/RI in diabetic mice as evidenced by decreased infarct size, cardiomyocyte apoptosis （ P 〈 0.01 ） and caspase-3 activity （ P 〈 0. 05 ）. RSV treatment also improved APN level both in plasma and adipose tissue in diabetic mice （ all P 〈 0.01 ）. Conversely, administration of AMPK inhibitor compound C significantly attenuated the cardioprotective

关 键 词：白藜芦醇 脂联素 缺血/再灌注损伤 Ⅱ型糖尿病 小鼠 

分 类 号：R587.1[医药卫生—内分泌]