Effect Of Estrogen On Hypoxia/Reoxygenation-induced Expression Of Adhesion Molecule Through NF-κB In Cardiac Myocytes

Myocardial ischemia-reperfusion can significantly increase the expression of ICAM-1 and VCAM-1, and indirectly induce inflammation-mediated myocardial injury. The increased expression of adhesion molecules induce the aggregation, adhesion of leukocyte, the release of a variety of inflammatory factors, and then produce sustained myocardial damage.NF-κB is a pleiotropic transcription factor existing in a variety of cells. many studies have proved that the nuclear factor NF-κB involves in inflammation, immunity, cell proliferation, apoptosis,pathological process, and myocardial ischemia/reperfusion injury.Phosphoeylation and degradation of IκB causes the NF-κB nuclear translocation, which may be the earliest and the most critical reason of the development of acute inflammation. Estrogen has a protective effect on myocardial injury, but the mechanism has not yet fully clear,the conclusion is not clear,either.In this paper, we established hypoxia/reoxygenation model using the primary cultured myocardial cells to simulate ischemia-reperfusion injury, We detected the rate of myocardial apoptosis in the condition of hypoxia/reoxygenation, as well as LDH, CK, MDA biochemical indicator. Western blot was used to detect the activation of NF-κB, and VCAM-1,ICAM-1 mRNA and protein expression were detected by RT-PCR and Elisa,respectively.Weapplied PDTC and ICI182,780 to interfere with the process of hypoxia, observed effect of E2 on the expression of NF-κB and adhesion molecules, and explored its possible mechanism.The results show that after hypoxia-4h/reoxygenation-4h, the rate of Cardiac cell apoptosis increased, NF-κB p65 into the nuclear is also significantly increased, as well as the expression of adhesion molecules.E2 can decrease the mRNA and protein expression of ICAM-1 and VCAM-1 by inhibit the activation of NF-κB, partly depending on ER path way. at the same time PDTC can significantly inhibit the activation of NF-κB and the expression of adhesion molecules, co-culture of E2 and PDTC inhibits their expressions more further, which shows that E2 also has Inhibitory effect on the adhesion molecules expression of non-NF-κB pathway In conclusion ,hypoxia/reoxygenation can promote NF-κB activation and enhance the expression of adhesion molecules, E2 can inhibit the expression of adhesion molecules through non-NF-κB and NF-κB path way.