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(10mg/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30min、再灌注3h或24h。抑制剂组于术前1h腹腔注射CompoundC(20mg/kg)。用TI'C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,Westernblot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CompoundC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