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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。
Objective To investigate the acute protective effect of 17b-estradiol (17b-E2) on myocardial ischemia / reperfusion (I / R) myocardium and its related mechanism. Methods Twenty-four healthy male New Zealand white rabbits were randomly divided into two groups (12 rats in each group) by means of ligation of left anterior descending coronary artery (LAD) Only), control group: 1ml of ethanol was injected into the anterior myocardial ischemia; experimental group: 10μg / kg of 17b-E2 was injected into the anterior myocardial ischemia. Serum levels of tumor necrosis factor-α (TNF-α) and leucocyte were detected by enzyme linked immunosorbent assay (ELISA) before myocardial ischemia, at 40 min of ischemia and at 1 h, 2 h and 3 h of reperfusion respectively. The content of IL-6 was detected by Western blotting. The expression of p38 mitogen-activated protein kinase (MAPK) in myocardium was detected by Western blotting. The expression of mitogen-activated protein kinase (MAPK) Cardiomyocyte apoptosis was detected by TUNEL method. Results During ischemia, the level of TNF-αin the experimental group was lower than that in the control group (F = 0.007, P = 0.001), while the change of IL-6 was not significant (F = 0.616, P = 0.095) The levels of p38MAPK and the apoptosis index in experimental group were significantly lower than those in control group (45.07% ± 2.73% vs.61.25% ± 2.41%, P <0.01) t = -15.398, P = 0.000; 11.21% ± 3.85% vs.22.02% ± 4.49%, t = -6.332, P = 0.000). Conclusion 17b-E2 attenuates myocardial I / R injury by inhibiting the inflammatory response and anti-apoptotic pathway, which may be through the inhibition of p38MAPK.