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Gender specific effect of progesterone on myocardial ischemia/reperfusion injury in rats.

机译:孕酮对大鼠心肌缺血/再灌注损伤的性别特异性作用。

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The study was designed to investigate the effect of progesterone and its gender based variation on myocardial ischemia/reperfusion (I/R) injury in rats. Adult Sprague Dawley rats were divided into vehicle treated reperfusion injury group male (I/R-M), female (I/R-F), ovariectomised (I/R-OVR) and progesterone treatment (I/R-M+PG, I/R-F+PG, I/R-OVR+PG) groups, respectively. I/R injury was produced by occluding the left descending coronary artery (LCA) for 1 h and followed by re-opening for 1 h. Progesterone (2 mg kg(-1) i.p.) was administered 30 min after induction of ischemia. Hemodynamic parameters (+/-dp/dt, MAP), heart rate, ST-segment elevation and occurrence of ventricular tachycardia (VT) were measured during the I/R period. The myocardial infarct area, oxidative stress markers, activities of myeloperoxidase (MPO) and creatine kinase (CK) were determined after the experiment along with the assessment of the effect on apoptotic activity by using DNA fragmentation analysis. Histological observationswere carried out on heart tissue. Treatment with progesterone significantly (P<0.05) reduced infarct area, lipid peroxidation (LPO) level and activity of MPO in females (I/R-F+PG) as compared to ischemic females (I/R-F). Progesterone significantly (P<0.001, P<0.05) inhibited serum CK activity and incidences of VT in female rats. Superoxide dismutase (SOD) activity, reduced glutathione (GSH) levels were significantly elevated (P<0.05) in I/R-F+PG group. Internucleosomal DNA fragmentation was less in I/R-F+PG group when compared to I/R-F group. The ischemic male and ovariectomised (I/R-M and I/R-OVR) counterparts did not show any significant change after progesterone treatment. In conclusion, the cardioprotective effect of progesterone on myocardial I/R injury induced damage is based on gender of the animal. The protective effect could be mediated by attenuation of inflammation and its possible interaction with endogenous estrogen.
机译:该研究旨在调查孕酮及其基于性别的变化对大鼠心肌缺血/再灌注(I / R)损伤的影响。成年Sprague Dawley大鼠分为媒介物处理的再灌注损伤组,雄性(I / RM),雌性(I / RF),去卵巢(I / R-OVR)和孕激素治疗(I / R-M + PG,I / R- F + PG,I / R-OVR + PG)组。闭塞左冠状动脉左冠状动脉(LCA)1小时,然后重新张开1 h,产生I / R损伤。诱导缺血后30分钟给予孕酮(2 mg kg(-1)i.p.)。在I / R期间测量血流动力学参数(+/- dp / dt,MAP),心率,ST段抬高和室性心动过速(VT)的发生。实验后测定心肌梗塞面积,氧化应激标志物,髓过氧化物酶(MPO)和肌酸激酶(CK)活性,并通过DNA片段分析评估对凋亡活性的影响。在心脏组织上进行组织学观察。与缺血女性(I / R-F)相比,女性(I / R-F + PG)孕酮治疗显着(P <0.05)减少了梗死面积,脂质过氧化(LPO)水平和MPO活性。孕酮显着(P <0.001,P <0.05)抑制雌性大鼠的血清CK活性和VT的发生。 I / R-F + PG组的超氧化物歧化酶(SOD)活性,降低的谷胱甘肽(GSH)水平显着升高(P <0.05)。与I / R-F组相比,I / R-F + PG组的核小体间DNA片段较少。孕酮治疗后,缺血性雄性和去卵巢(I / R-M和I / R-OVR)对应物未显示任何显着变化。总之,孕酮对心肌I / R损伤引起的损伤的心脏保护作用基于动物的性别。保护作用可以通过减轻炎症及其与内源性雌激素的相互作用来介导。

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