淫羊藿总黄酮对大鼠心肌急性缺血再灌注损伤氧化应激干预机制的研究

观察淫羊藿总黄酮(total flavones of Epimedium,TFE)对大鼠心肌急性缺血再灌注损伤氧化应激干预作用及其机制。40只雄性大鼠随机分为假手术组,模型组,地尔硫卓组(阳性对照药)以及淫羊藿总黄酮高、低剂量组,每组8只。淫羊藿总黄酮分别以200,100 mg·kg~(-1)的剂量连续灌胃给药4 d后,结扎冠状动脉前降支40 min再灌注4 h建立大鼠急性心肌缺血再灌注损伤模型。采用N-BT染色法测定心肌梗死范围,比色法检测心肌组织中SOD和T-AOC活性及MDA含量,ELISA法测定血清Tn I水平,同时光镜下观察心肌组织结构的变化,分别应用免疫组化和Western blot法观察心肌组织中SIRT1与Nrf2表达的变化。结果发现,与模型组比较,淫羊藿总黄酮高、低剂量组以及地尔硫卓组能明显减少心肌梗死范围,降低血清Tn I水平,提高心肌组织中SOD和T-AOC活性并降低MDA含量(P0.05或P0.01),改善缺血再灌注损伤后心肌的组织结构,同时淫羊藿总黄酮高、低剂量组中心肌组织SIRT1和Nrf2表达明显增加(P0.05或P0.01)。由此可见,淫羊藿总黄酮能够通过提高机体SIRT1与Nrf2内源性抗氧化信号传导通路,增加心肌组织的抗过氧化能力,从而抑制心肌急性缺血再灌注过程中氧化应激反应导致的心肌细胞不可逆性伤害,维护心肌组织的正常功能。

Mechanisms of total flavones of Epimedium on oxidative stress induced by myocardial ischemia/reperfusion injury in rats

To investigate the effects and mechanisms of total flavones of Epimedium (TFE) on oxidative stress induced by myocardial ischemia/reperfusion injury in rats, forty male SD rats were randomly divided into sham operated group, model group, diltiazem group and flavonoids of Epimedium low and high doses groups with 8 rats in each. Myocardial ischemia/reperfusion injury model was induced by ligaturing the left anterior descending artery for 30 min followed reperfusion for 4 h after TFE was taken by intragastric administration for 4 days. The degree of myocardial infarct was observed by N-BT staining. The concentrations of MDA and activities of SOD and T-AOC in cardiac tissue were measured by colorimetry. Serum TnI concentrations were checked by ELISA. HE stain was used to observe myocardium structure under light microscope. Expressions of SIRT1 and Nrf2 in cardiac tissue were evaluated by immunohistochemistry method and Western blot, respectively. Compared with the model group, the degree of myocardial infarct, MDA concentration in cardiac tissue and the levels of TnI in serum significantly decreased in the diltiazem group and flavonoids of Epimedium low and high doses groups (P<0.05 or P<0.01); flavonoids of Epimedium low and high doses groups and the diltiazem group also showed improvements in myocardium structure under ischemia/reperfusion injury. TFE significantly increased the activity of SOD and T-AOC and the expression of SIRT1 and Nrf2 in cardiac tissue when compared with the model group (P<0.05 or P<0.01). Therefore, TFE can increase anti-peroxidant capacity of myocardium tissue by using intrinsically anti-oxidant signaling pathway of SIRT1 and Nrf2, which can inhibit irreversible damage of cardiomyocytes in myocardial ischemia/reperfusion injury and protect normal function of cardiac tissue.