RESUMO
Objective To study the protective effect of trimetazidine pretreatment on myocardial I/R in a rat I/R model and its mechanism.Methods One hundred and twenty SD rats were divided into control group,I/R group,HSP70 inhibitor group,trimetazidine treatment group and combined treatment group (24 in each group).The rats in each group were further divided into 30 min reperfusion group,4 h reperfusion group and 8 h reperfusion group (8 in each group).Their HSP70-positive myocardial cells were calculated,their serum CK,CK-MB,MDA,SOD levels and their myocardial infarction size were measured.Results The serum CK and CK-MB levels were significantly higher in I/R group,HSP70 inhibitor group,trimetazidine treatment group and combined treatment group than in control group and were significantly lower in trimetazidine treatment group than in combined treatment group and I/R group after reperfusion for 4 and 8 h (P＜0.01).The serum levels of HSP70 and SOD were significantly higher,the MDA levels were significantly lower in trimetazidine treatment group than in combined treatment group and I/R group after reperfusion for 30 min,4 and 8 h (P＜0.01).The infraction size was significantly smaller in trimetazidine treatment group than in combined treatment group and I/R group after reperfusion for 4 and 8 h (P＜0.05).Conclusion Trimetazidine can increase the serum HSP70 level in myocardial cells,reduce the infarction size,and protect the myocardium against I/R in rats.
RESUMO
Objective To investigate the effects of rapamycin on the number and function of peripheral blood endothelial progenitor cells (EPCs). Methods Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation, and then the cells were plated on fibronectin-coated culture dishes. After 7-day culture, adherent cells were treated with rapamycin in a series of final concentrations of 1.0, 2.0, 5.0?g/ml for 6, 12, 24, and 48h. EPCs were identified as adherent cells double positive for DiLDL-uptake and lectin binding by direct fluorescent staining as demonstrated under a laser scanning confocal microscope. EPCs were further documented by demonstrating the expression of VEGFR-2, AC133 and CD34 with flow cytometry. EPCs proliferation and migration were assayed with MTT assay and modified Boyden chamber assay, respectively. EPCs adhesion assay was performed by replating them on fibronectin-coated dishes, and then adherent cells were counted. In vitro vasculogenesis activity was assayed by in vitro vasculogenesis kit. Results Incubation of isolated human MNCs with rapamycin resulted in a decrease in the number of EPCs, and rapamycin also decreased EPCs proliferative, migratory, adhesive and in vitro vasculogenesis capacity in both concentration and time dependent manners. Conclusion Rapamycin decreases the number, proliferative, migratory, adhesive and in vitro vasculogenesis capacity of EPCs.
