Department of Anesthesiology, Chang Gung Memorial Hospital, Chang Gung University, Tao-Yuan, Taiwan.
J Surg Res. 2012 Jul;176(1):171-7. doi: 10.1016/j.jss.2011.05.039. Epub 2011 Jun 22.
Resveratrol has been shown to have protective effects for patients in shock-like states, and Akt (protein kinase B) is known to play a role in pro-inflammatory events in response to injury. The aim of this study is to determine whether resveratrol provides cardioprotection mediated via an Akt-dependent pathway in trauma-hemorrhaged animals.
Male Sprague-Dawley rats underwent trauma-hemorrhage and resuscitation. A single dose of resveratrol (30 mg/kg body weight) with or without a PI3K inhibitor (wortmannin) or vehicle was administered intravenously during the resuscitation. Two hours after either the trauma-hemorrhage or sham operation, the cardiac output, the positive maximal pressure increase of the left ventricle (+dP/dt(max)), and the negative maximal pressure decrease of the left ventricle (-dP/dt(max)) were measured. Cardiac myeloperoxidase (MPO) activity, interleukin (IL)-6, and intercellular adhesion molecule (ICAM)-1 levels, Akt activity, and apoptosis were measured. One-way ANOVA and Tukey's test were used for statistical analysis.
Cardiac output and ± dP/dt(max) decreased significantly after trauma-hemorrhage. Administration of resveratrol significantly improved these cardiac function parameters. Trauma-hemorrhage increased cardiac MPO activity, IL-6 levels, and ICAM-1 levels, and these parameters were significantly improved in the resveratrol-treated rats subjected to trauma-hemorrhage. Although trauma-hemorrhage decreased cardiac Akt phosphorylation (p-Akt), resveratrol treatment following trauma-hemorrhage prevented the same decrease in cardiac p-Akt. The increase in cardiac apoptosis was attenuated in rats that received resveratrol. Co-administration of wortmannin prevented the beneficial effects of resveratrol on the attenuation of pro-inflammatory responses and cardiac injury after trauma-hemorrhage.
Resveratrol attenuates cardiac injury following trauma-hemorrhage, which is, at least in part, due to its anti-inflammatory effects via Akt-dependent pathways.
白藜芦醇已被证明对类似休克状态的患者具有保护作用，而 Akt（蛋白激酶 B）已知在受伤后炎症反应中发挥作用。本研究旨在确定白藜芦醇是否通过创伤性出血动物中的 Akt 依赖性途径提供心脏保护。
雄性 Sprague-Dawley 大鼠接受创伤性出血和复苏。在复苏期间，静脉内给予白藜芦醇（30mg/kg 体重）单剂量，或同时给予 PI3K 抑制剂（wortmannin）或载体。在创伤性出血或假手术后 2 小时，测量心输出量、左心室正最大压力升高（+dP/dt(max)）和左心室负最大压力降低（-dP/dt(max)）。测量心脏髓过氧化物酶（MPO）活性、白细胞介素（IL）-6 和细胞间黏附分子（ICAM）-1 水平、Akt 活性和细胞凋亡。使用单因素方差分析和 Tukey 检验进行统计分析。
创伤性出血后心输出量和±dP/dt(max)明显下降。给予白藜芦醇可显著改善这些心功能参数。创伤性出血增加了心脏 MPO 活性、IL-6 水平和 ICAM-1 水平，而在创伤性出血后接受白藜芦醇治疗的大鼠中，这些参数得到了显著改善。尽管创伤性出血降低了心脏 Akt 磷酸化（p-Akt），但创伤性出血后给予白藜芦醇治疗可防止心脏 p-Akt 的相同降低。接受白藜芦醇的大鼠心脏细胞凋亡增加减少。wortmannin 的共同给药可防止白藜芦醇对创伤性出血后抗炎反应和心脏损伤的有益作用。
白藜芦醇可减轻创伤性出血后的心脏损伤，至少部分原因是通过 Akt 依赖性途径发挥抗炎作用。
