Experimental Study On The Effects Of Tubastatin A On Attenuating Myocardial Damage In Sepsis By Reducing Oxidative Stress

Objective: Sepsis is one of the most common diseases in the emergency department.40% to 50% of patients with sepsis can have myocardial inhibition,and 7% will have heart failure.Heart is one of the most vulnerable target organs of sepsis.In sepsis,pathogen-related molecular patterns in circulation and injury-related molecular patterns act together on cardiomyocytes to induce a large number of intracellular ROS.Excessive ROS causes oxidative stress injury of cardiomyocytes.Tubastatin A has been shown to improve long-term survival in rats with fatal sepsis by reducing ROS production in astrocytes,mammary epithelial cells,and cardiomyocytes stimulated by hyperglycemia and hypoxia/reoxygenation in sepsis models,alleviating oxidative stress damage,and playing a protective role in cells.To study the role of Tubastatin A(Tub A)on the oxidative stress damage caused by inflammatory cytokines produced by LPS-stimulated macrophages(RAW264.7).Methods: The rat H9C2 myocardial cells were divided into three groups: the SHAM group was cultured by the macrophages cell culture fluid without LPS stimulation,the MCM group was cultured by the macrophages cell culture fluid with LPS stimulation,the Tub A group was pretreated with Tub A and then was cultured by the macrophages cell culture fluid containing Tub A,which acquired from the macrophages with LPS stimulation.After culturing the three groups of myocardial cells for 24 hours,detecting cell activity,cell oxidative stress levels and the concentration of myocardial damage markers in the cell culture fluid.Results: The concentration of NO in the macrophages cell culture fluid which MCM group was cultured was significantly higher than that SHAM group was cultured.Compared with the SHAM group,the level of reactive oxygen species(ROS)and lipid peroxidation product malondialdehyde(MDA)in cardiomyocytes increased significantly,the activity of myocardial cells was significantly decreased,the level of lactic acid dehydrogenase(LDH)and creatine kinase-MB(CK-MB)which were released by myocardial cells significantly increased.Compared with the MCM group,the content of ROS and MDA in the Tub A group had decreased significantly,the cells activity was significantly higher,the release of LDH was significantly reduced.The release of CKMB showed a downward trend.Conclusion: Tub A protects the cardiomyocytes from oxidative stress damage caused by inflammatory cytokines produced by LPS-stimulated macrophages.