The Effect Of Cholesterol Level Changes On The Apoptosis Of Myocardial In Myocarditis And Its Mechanism

[Objective]The previous study found that the level of HDL in patients with myocarditis decreased,could lead to the accumulation of cholesterol in the tissues.This research is to study the effect of abnormal cholesterol level in myocarditis on cardiomyocyte apoptosis and its mechanish,and provide a new method for clinical diagnose and treatment.[Methods]This study was divided into three parts:(Ⅰ)Animal experiment:The model of EAM was used to analyze the changes of serum lipid levels and cholesterol levels in myocardium of rats with myocarditis.(Ⅱ)Intervention experiments:Reduced the level of cholesterol in cardiomyocytes by using MCβD,then compare the degree of myocardial injury、inflammation level and cardiomyocyte apoptosis with the rats of EAM group.(Ⅲ)Cell experiment:In order to verify the results of animal experiment,we couducted cell experiment,induced H9C2 cells with cholesterol and confirmed the effects of elevated cholesterol levels on apoptosis of H9C2 cells and its mechanish.[Results](Ⅰ)Animal experiments:Compared with the control group,the level of serum HDL decreased significantly in two weeks of EAM,we also found the accumulation of cholesterol in myocardium.(Ⅱ)Intervention experiments:Using MβCD to reduce the content of cholesterol in cardiomyocytes can decrease the degree of cardiomyocyte apoptosis and the expression of apoptotic factors cleaved caspase-3,Fas,FasL and Bax/Bcl-2,the expression of phospho-P38 decreased and phospho-ERK increased.(Ⅲ)Cell experiment:The results showed that increased the cholesterol content of H9C2 could promote cardiomyocyte apoptosis,promote the expression of apoptotic factors cleaved caspase-3,Fas,FasL and Bax/bcl-2,and inhibit the expression of phospho-P38 and increase the expression of phospho-ERK.[Conclusion]The content of serum HDL was decreased in myocarditis,meanwhile,there was significant accumulation of cholesterol in the cardiomyocytes.Both animal and cell experiments proved that increasing intracellular cholesterol content could promote apoptosis and decreasing intracellular cholesterol content could inhibit the apoptosis of cardiomyocyte.The effect of cholesterol on cardiomyocyte apoptosis was probably through two pathways,one was through the Fas and FasL pathway,the other was influencing the expression of Bax/Bcl-2 through the P38 and ERK MAPK pathway.