Molecular Mechanism Of Melatonin In Preventing Cardiovascular Injury In Chronic Intermittent Hypoxia Rats Of OSAHS

Objective Explore how MLT affects the arteries,MLCK expression and activity in OSAHS rats with chronic intermittent hypoxia;Which MAPK channel protein is used by MLT to affect MLCK.Provide relevant theories for the treatment of OSAHS patients and the prevention of CVDs.Methods Take 30 healthy rats and divide them into three groupss: normal control group,CIH group,MLT treatment group.Rat model OSAHS chronic intermittent hypoxia and MLT therapy with hypoxemia chamber,Blood samples were collected to detect the melatonin concentration,cardiovascular disease-related inflammatory factor concentration and ROS level in the three groups of rats,and the macromolecular fluorescent dye permeation method was used to analyze the changes in arterial intima permeability.Detect the expression and activity of MLCK in the arterial wall of the three groups of rats,the transcription,expression and respective phosphorylation levels of MAPK pathway proteins.Analyze the impact of MLT on the above results.In the cell experiment,primary cultured rat aortic endothelial cells were cultured in vitro to simulate chronic intermittent hypoxia.Normal group,pure hypoxia group,HRO group,and MLT treatment group.Detect the ROS level and permeability of the four groups of arterial endothelial cells,and the transcription level of the MAPK signal transduction pathway protein,and then add different MAPK pathway protein specific inhibitors SB203580,PD98059 and curcumin form a new grouping situation: normal control group,pure hypoxia group,HRO group,MLT treatment group,HRO+SB203580group,MLT+SB203580 group,HRO+PD98059 group,MLT+PD98059 group,HRO+curcumin group,MLT+curcumin group.Then detect and compare the activity of MLCK in arterial endothelial cells,the level of MAPK signal proteins,and analyze the influence of MLT on the above results of arterial endothelial cells,and analyze the effects of MLT and specific channel inhibitors on different MAPK signal transduction The pathway protein influences the relevance of MLCK expression activity.Results Elevated blood and arterial endothelial cell ROS in chronic intermittent hypoxia rats,MLT treatment reduced ROS levels(compared with CIH group),P<0.05);MLT protects the arterial wall and endothelial cells of chronic intermittent hypoxia rats,Can reduce the permeability of the intima and cells,Repair of intimal barrier function,Improved arterial damage;Compared with the normal control group,MLCK expression and activity of arterial wall and endothelial cells in chronic intermittent hypoxia rats,MLCK expression can be reduced by MLT treatment,decreased activity(P<0.05);MLT SB203580 、 PD98059 synergistic effect with specific inhibitors p38 、 ERK signal transduction proteins,MLT can regulate the expression of MLCK through p38/MAPK、ERK/MAPK channel pathway and improve cardiovascular injury in rats.Conclusion OSAHS model of chronic intermittent hypoxia rats was established successfully;MLT can reduce ROS,and the permeability of intima and protect the intimal barrier in chronic intermittent hypoxia rats;MLT,the expression and activity of arterial wall and endothelial cells in chronic intermittent hypoxia rats are reduced by regulating the p38/MAPK、ERK/MAPK pathway in the MAPK pathway,which can protect the arterial endothelial cytoskeleton and improve the cardiovascular injury of chronic intermittent hypoxia rats.