【摘要】 目的探讨17b-雌二醇(17b-E2)对兔在体缺血/再灌注(I/R)心肌的急性保护作用及其相关机制。方法通过结扎冠状动脉左前降支建立兔在体心肌I/R模型(心肌缺血40 min,再灌注3 h);采用抽签法将24只健康雄性新西兰白兔随机分为两组(每组12只),对照组:心肌缺血前静脉注入1 ml乙醇;实验组:心肌缺血前静脉注入10μg/kg 17b-E2。用酶联免疫吸附测定(ELISA)法分别于心肌缺血前、缺血40 min、再灌注1 h、2 h和3 h不同时间点检测血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的含量;蛋白印迹法(Western blotting)测定心肌p38丝裂原活化蛋白激酶(MAPK)的表达;脱氧核苷酸转移酶介导的生物素脱氧尿嘧啶核苷酸缺口末端标记(TUNEL)法检测心肌细胞凋亡。结果缺血过程中,实验组TNF-α较对照组降低(F=0.007,P=0.001),而IL-6变化不明显(F=0.616,P=0.095);再灌注过程中,实验组TNF-α和IL-6的含量明显低于对照组(P<0.01);同时实验组p38MAPK的活性和心肌凋亡指数均明显低于对照组(45.07%±2.73%vs.61.25%±2.41%,t=-15.398,P=0.000;11.21%±3.85%vs.22.02%±4.49%,t=-6.332,P=0.000)。结论 17b-E2通过抑制炎症反应及抗凋亡途径减轻心肌I/R损伤,其作用可能是通过对p38MAPK的抑制而实现的。更多还原

【Abstract】 Objective To investigate the acute cardioprotective effect of 17b-estradiol(17b-E2) against severe myocardial ischemia/reperfusion(I/R) injury in rabbits and the mechanism of the effect.Methods We established the model of myocardial I/R in vivo by occluding the left anterior descending coronary artery of the rabbits(who underwent coronary occlusion for 40 minutes followed by 3 hours of reperfusion).Twenty-four New Zealand white male rabbits were randomly divided into two groups with 12 in each group. Before coronary occlusion,1 ml of ethanol or 17b-E2 at 10 μg/kg was administered intravenously to the rabbits in the control group and the experimental group respectively.The serum levels of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were measured by enzyme-linked immunosorbent assay(ELISA) at the following time points: before occlusion,40 minutes after occlusion,1 hour,2 hours and 3 hours after reperfusion.Activation of p38 mitogen activated protein kinase(MAPK) was determined by Western blotting analysis,and apoptosis of cardiocytes was identified by terminal deoxynucleotidlyl transferase mediated deoxyuridine-biotin dUTP Nick End Labeline(TdT)-mediated dNTP nick end labeling(TUNEL) staining.Results During myocardial ischemia,TNF-α decreased significantly in the experimental group compared with the control group(F=0.007,P=0.001),while there was no difference in IL-6 between the two groups(F=0.616,P=0.095).During the process of reperfusion,the levels of TNF-α and IL-6 in the experimental group were significantly lower than those in the control group(P<0.01).Besides,the activation of p38 MAPK and apoptotic index for the experimental group were also lower(45.07%±2.73% vs. 61.25%±2.41%,t=-15.398,P=0.000;11.21%±3.85% vs.22.02%±4.49%,t=-6.332,P=0.000).Conclusion The cardioprotective effect of 17b-E2 against myocardial I/R may be attributed to its anti-inflammatory and anti-apoptotic properties,which is probably associated with the inhibition of 17b-E2 on p38MAPK activity.更多还原