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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。
Objective: To investigate the effect of resveratrol (RSV) on myocardial ischemia / reperfusion injury (MI / RI) and its mechanism in type 2 diabetes mellitus (T2DM) mice. Methods: A T2DM mouse model was established by feeding a high-fat diet combined with low-dose streptozotocin (STZ). Immediately after RSV (10 mg / kg) was given orally once a day for 3 consecutive weeks after successful modeling. The experiment was divided into normal sham operation group, normal operation control group, DM sham operation group, DM operation control group, RSV group and CpC group, with 20 rats in each group. Surgical methods using left anterior descending coronary artery ligation for 30 min, reperfusion 3 h or 24 h. The inhibitor group was injected with Compound C (20 mg / kg) intraperitoneally 1 h before surgery. The area of myocardial infarction (MI) was detected by TTC staining, cardiomyocyte apoptosis was detected by TUNEL, the activity of caspase-3 and the level of plasma adiponectin (APN) were measured by ELISA. The expressions of AMPK, p-AMPK and adipose tissue APN Content. Results: T2DM mice were successfully established by feeding a high-fat diet combined with low-dose STZ. Compared with the DM operation control group, RSV feeding could reduce the MI / RI, MI area and the cardiomyocyte apoptosis (P <0.01), and decrease the activity of caspase-3 in T2DM mice (P <0.05). RSV could also up-regulate the expression of APN in adipose tissue and reverse the low APNmia in T2DM mice (P <0.01). Compound C, an AMPK inhibitor, significantly attenuated myocardial protection of RSV (P <0.05). Conclusion: RSV can protect myocardium by reversing the hypoglycemia in T2DM mice.