Effect of Diazoxide on Myocardial Cell Apoptosis and Inflammatory Response in Rats with Coronary Heart Disease and Its Mechanism
Objective:To investigate the effect of diazoxide on cardiomyocyte apoptosis and inflammatory response in rats with coronary heart disease(CHD).Methods:SD rats were divided into model group,diazoxide low-dose group,diazoxide medium-dose group,and diazoxide high-dose group.Normal rats served as the blank control group,and the rats in diazoxide low-dose group,medium-dose group,high-dose group were administered 3,5,and 7 mg/kg of diazoxide by gavage respectively.After 14 days of treatment,serum levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,IL-6,triglyceride(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and 3-hydroxy-3-methylglutaryl-coenzyme A reductase(HMGR)were measured.Hematoxylin-eosin(HE)staining was used to observe myocardial tissue injury.Western Blot was used to detect Bax,Cleaved Caspase-3,Bcl-2,glyceraldehyde-3-phosphate dehydrogenase(GAPDH),nuclear factor-κB(NF-κB),phosphorylated NF-κB(p-NF-κB),peroxisome proliferator-activated receptor y(PPARy).Results:Compared with the model group,the serum levels of IL-1β,IL-6,TG,TC,LDL-C,HDL-C,and HMGR were significantly lower in the diazoxide low-dose group,middle dose group,and high-dose group.Additionally,myocardial cell damage was significantly reduced and the expression of apoptosis-related proteins Bax and Cleaved Caspase-3 was down-regulated.The expression of Bcl-2 was significantly up-regulated while the expression of p-NF-κB was significantly decreased.Furthermore,the expression of PPARγ was significantly up-regulated(P＜0.05).Conclusion:Diazoxide can significantly alleviate myocardial injury in CHD rats,and its mechanism may relate the regulation of PPAR γ and NF-κB signal pathway.
coronary heart diseasediazoxidemyocardial apoptosisinflammatory responseblood lipidexperimental study
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