Effects Of SAHA On Myocardial Reperf Usion Injury

Reperfusion therapy is an important life-saving measure in patients with acute myocardial infarction..Myocardial ischemia reperfusion injury(MIRI)has become an important problem hindering the benefit from reperfusion therapy in ischemicmyocardium.Histone deacetylase(HDAC)is an important post-translational modification enzyme,the status and degree of histone deacetylation is closely related to a variety of cardiovascular diseases.Suberoylanilide hydroxamic acid(SAHA)is a class of HDAC small molecular inhibitors approved by the us food and drug administration of USA(FDA)for clinical applications,it effects on myocardial ischemia reperfusion injury has not been reported.In this paper,an animal model of myocardial ischemia reperfusion injury was established to explore whether SAHA has a protective effect on myocardial ischemia reperfusion.Objectives: To observe the mechenism of the effect of SAHA on myocardial ischemia reperfusion injury in mouse.Methods: Male C57BL/6 mice were selected as the study subjects,and the experimental animals were completely randomly assigned into four groups: group 1,normal control Sham +DMSO.Group 2,normal control Sham operation(Sham)+SAHA50mg/kg;Group 3,ischemia reperfusion(I/R)+DMSO;Group 4,ischemia reperfusion(I/R)+SAHA50mg/kg.A mouse model of myocardial ischemia reperfusion was established by ligating the left anterior descending branch of the coronary artery for 45 minutes and then releasing the live node at the ligation site.In the sham group,the mice were treated with ischemia reperfusion except that the nodule was not ligated at the anterior descending branch.Echocardiography was performed 24 hours after reperfusion.The myocardial enzyme levels of CK-MB and LDH were determined by direct method.The range of myocardial infarction was calculated by weighing method after double staining with Evansblue/TTC.Results: 1.Echocardiographic results: after myocardial ischemia-reperfusion injury,LVEF decreased significantly,LVDd increased,LVDs increased,and LVFS decreased(I/R+DMSO group vs.sham+DMSO group,P< 0.05).After SAHA50mg/kg,LVEF increased,LVDd decreased,and LVDs decreased(I/R+SAHA group vs.I/R+DMSO group,P<0.05).SAHA had no significant effect on echocardiographic results in the sham group(sham+DMSO group vs.sham+SAHA group,P<0.05).2.Direct measurement of myocardial enzymes: compared with sham group,CK-MB and LDH increased after ischemia reperfusion injury(I/R+DMSO group vs.sham+DMSO group,P< 0.05).After SAHA50mg/kg,CK-MB and LDH of I/R group decreased(I/R+SAHA group vs.I/R+DMSO group,P<0.05).There was a slight increase in CK-MB and LDH in the sham group,but no statistical difference was found in the results of adding SAHA 50mg/kg(sham+DMSO group vs.sham+SAHA group,P>0.05).3.Evans blue/TTC double staining was used to determine the increased proportion of myocardial infarction after ischemia reperfusion injury(I/R+DMSO group vs.sham+DMSO group,P<0.05).Myocardial infarction decreased after SAHA50mg/kg administration,and the difference was statistically significant(I/R+SAHA group vs.I/R+DMSO group,P<0.05).The proportion of myocardial infarction was small in the sham group,and SAHA50mg/kg was not statistically significant for the results(sham+DMSO group vs.sham+SAHA group,P > 0.05).Conclusions: When the myocardial tissue is in a non-hypoxic state,the application of SAHA cannot improve the damage of myocardial cells.The application of SAHA before myocardial ischemia reperfusion in mice can improve myocardial function after reperfusion injury,lower serum myocardial enzyme and improve infarction area,reduce myocardial ischemia reperfusion injury,play a protective role.