The Effect Of Estrogen On The Activation Of Nrf2 And The Expression Of HO-1 And Cu/Zn-SOD

Oxygen free radicals (ROS) cause of myocardial ischemia-reperfusion injury-induced apoptosis is one of the important material, but Nrf2 / ARE antioxidant system in the process of scavenging oxygen free radicals play an important role.The activated Nrf2 can transport into the nucleus, and bind with the effect of the downstream target genes of a multi-ARE b, its transcripts includ superoxide dismutase (SOD), heme oxygenase (HO-1), thioredoxin (Thioredoxin) and PhaseⅡdetoxification enzymes, such as glutathione S-transferase (GST) . These enzymes can effectively remove oxygen free radicals within cells to maintain intracellular steady-state situation. Estrogen has a wide range of anti-oxidant role in cardiovascular protection and an important physiological significance, while its mechanism is different, not very clear, especially for the role of pathways in the theory is still worth studying. In this study, using primary culture of cardiac cells, through the establishment of hypoxia / reoxygenation (H / R) model to simulate myocardial ischemia / reperfusion injury model, to a certain dose of exogenous estrogen(5μM) to study whether the effect of in the course of its anti-oxidation in the hypoxia / reoxygenation is associated with Nrf2 / ARE antioxidant system. Experiment found that the survival rate of decline in myocardial cells, Caspase-3 levels, the number of cells in late apoptosis and ROS generation of hypoxia / reoxygenation model group was significantly higher than control group. The cells are in a state of oxidative damage. In the process of hypoxia / reoxygenation, the cells which added estrogen, the degree of injury was improved. ROS was significantly reduced. The amount of transcription factor Nrf2 in the nuclear and the expression of mRNA or protein of heme oxygenase and superoxide dismutase are higher than those in the injury group. Prior to joining estrogen inhibitor, the effect of estrogen goes away. Conclusion: In the process of hypoxia / reoxygenation, estrogencan promote the nuclear transcription factor Nrf2 into the nucleus, so that the expression of the downstream clear two kinds of protective enzyme HO-1 and Cu / Zn-SOD increased, a large number of Oxygen free radicals have been removed, so that the rate of apoptosis were declined and the activity was increased, thereby protecting myocardial cells from oxygen free radicals attacks, reduced injury in the process of hypoxia / reoxygenation.