The Expression Of COX-2 And Apoptosis In The Acute Hypoxia Myocardium

Objective: To investigate the expression of cyclooxygenase-2 (COX-2) and apoptosis in myocardium induced by acute hypoxia, and to study the possible effects of COX-2 inhibitor on this progress.Methods: The rabbit model of myocardial acute hypoxia has been done by ligating the left anterior descending coronary artery and the culture rat myocardial cell model of hypoxia has been done by changing the concentration of O2 in the incubator. The expression of COX-2 was observed on the pathological sections by monoclonal antibody immunohistochemistry staining in acute hypoxia in situ myocardium and culture myocardial cell, and the effects of intervened COX-2 inhibitors (rofecoxib and NS-398) and aspirin were observed separately. The expression of COX-1,-2 were analyzed by Western-Blot. The changes of TXB2 and 6-keto-PGFia were measured with radioimmunoassay in serum, tissue and cells culture fluid, the apoptosis of myocardial cell induced by acute hypoxia and the effects of apoptosis intervened COX-2 inhibitors were determined by flow cytometer and TUNEL method, Results: COX-2 but not COX-1 was induced expression in myocardium by acute hypoxia. The increasing levels of TXB2 and 6-keto-PGFia and augmenting the ratio of TXB2 / 6-keto-PGF1 were induced by acute hypoxia. Both of COX-2 inhibitors and aspirin could be lower the productions of TXB2 and 6-keto-PGF1 in serum. COX-2 inhibitors were more effective on 6-keto-PGF1 in situ myocardium and serum, but aspirin was more effective on TXB2 than COX-2 inhibitors in serum, situ myocardium and cells culture fluid. The results have come out that COX-2 inhibitors enhanced the augment of ratio of TXB2 / 6-keto-PGFia in serum and aspirin inhibited the increase of ratio of TXB2 / 6-keto-PGF1 in serum and situ myocardium. The apoptosis of myocardium could be induced by acute hypoxia in situ myocardium and culture3myocardial cell. And COX-2 inhibitors could promote myocardium apoptosis. Conclusions: This research indicated that COX-2 may be directly induced by acute hypoxia. The COX-2 inhibitors used in this study were effective in blocking the increase in COX-2 activity and production of PGs and TXA2 associate with acute hypoxia. The apoptosis could be induced by acute hypoxia in situ myocardium and culture myocardial cell, which could be advanced by COX-2 inhibitors. And they enhanced the augment of ratio of TXBa / 6-keto-PGFia in serum and aspirin inhibited the increase of ratio of TXB2 / 6-keto-PGFia in serum and in situ myocardium, suggested that COX-2 inhibitors had potential side effect of cardiovascular diseases and aspirin had cardio protective action.