Protective Effect Of Histone Deacetylase Inhibitor SAHA On Intermittent Hypoxia-induced Cardiovascular Injury In Mice

Background Obstructive sleep apnea(OSA)is a common condition characterized by paroxysmal upper airway narrowing during sleep leading to intermittent hypoxia(IH)and sleep disruption.This is an independent risk factor for cardiovascular disease.IH is closely related to hypertension,increased sympathetic activity,endothelial dysfunction,oxidative stress,and systemic inflammation,and is the most important factor causing cardiovascular disease.Studies have shown that epigenetic processes mediated by histone deacetylases(HDACs)play an important regulatory role in the development of cardiovascular diseases,and inhibition of HDAC plays an important role in cardiovascular protection and can become cardiovascular New methods for the diagnosis and treatment of diseases.The purpose of this study was to investigate the protective effect and mechanism of HDAC inhibitor SAHA on intermittent hypoxiainduced cardiovascular injury in mice.Aim 1.Through the establishment of IH mouse model,application of HDAC inhibitor SAHA,to observe whether SAHA IH mice vascular endothelial damage function improved.2.By using HDAC inhibitor SAHA,the cardiac remodeling of IH mice was observed,and whether cardiac remodeling after SAHA treatment was inhibited.3.To explore the mechanisms by which SAHA may affect the cardiovascular system,such as the regulation of e NOS and inhibition of the production of reactive oxygen species.MethodsThe mice were divided into four groups: normal oxygen(Sham)group,intermittent hypoxia(IH)group,normal oxygen SAHA intervention(Sham+SAHA)group,and intermittent hypoxic SAHA intervention(IH+SAHA)group.The vasoconstriction and diastolic function of the common carotid artery and thoracic aorta in mice were measured by vascular tone measurement.Cardiac hypertrophy and myocardial remodeling were detected by measuring the heart weight and pathology,and the reactive oxygen species in the heart were detected by DHE staining.Results 1.Vascular endothelium-dependent diastolic function is impaired in intermittent hypoxic mice,while HDAC inhibitor SAHA protects endothelial dysfunction caused by intermittent hypoxia,whereas the four groups of mice have endothelial endotheliumindependent dilation Not affected.2.Intermittent hypoxia can make myocardial cells hypertrophy,and SAHA can inhibit myocardial hypertrophy caused by intermittent hypoxia.3.Intermittent hypoxia can significantly increase the degree of myocardial fibrosis,and SAHA can inhibit myocardial fibrosis caused by intermittent hypoxia.4.Intermittent hypoxia increases reactive oxygen species in cardiomyocytes,and SAHA can inhibit the production of reactive oxygen species in cardiomyocytes caused by intermittent hypoxia.Conclusion Intermittent hypoxia can cause an increase in cardiovascular reactive oxygen species and lead to vascular endothelial dysfunction,myocardial cell hypertrophy and fibrosis,while acetylase inhibitors can protect against intermittent cardiovascular damage.