Influences Of Granulocyte Colony-Stimulating Factor On Adriamycin-Induced Myocardium Injury In Rats.

Objective:It has not been well-known yet how Granulocyte Colony-Stimulating Factor(G-CSF)affects nonischemic cardiomyopathy,though its beneficial effects on acute myocardial infarction(AMI)are confirmed by several studies.Our aim was to detect the influence of G-CSF on cardiac function of adriamycin-induced cardiotoxicity in rats and to explore the possible mechanism of the bone marrow stem cells(BMSCs)auto-mobilized by G-CSF can recruit into damaged myocardium.Methods and Materials:Healthy male Wistar rats were randomly grouped into control,ADR,ADR+G-CSF group(n=12 in each group).ADR(2.5mg/kg,6 times for 2 weeks)was administered intraperitoneally in all rats except the control group. After 24 hours of final treatment,the rats in ADR+G-CSF group were injected with G-CSF(50μg/kg/day for 8days)subcutaneously.G-CSF was substituted by NS in ADR group.Cardiac function was evaluated by cardiac catherization after 4 weeks. Then,all animals were sacrificed and hearts were fixed with 4%parafermaldehyde. Tissue were used for histological and immunohestochimical analysis. Cardiomyocytes apoptosis was also detected by in situ terminal deoxynucleotidyl transferase assay(TUNEL method).Results:The ADR and ADR+G-CSF groups showed significant deteriorations of cardiac function and high cardiomyocyte apoptosis index compared with control group.Hemodynamics compared with the ADR group,the ADR+G-CSF group showed significant higher LVSP(12.65±2.34Kpa vs10.95±1.51Kpa,p＜0.05). Though other hemodynamic parameters had no statistical difference between ADR+G-CSF and ADR groups,DAP(7.98±2.19Kpa vs8.01±1.54Kpa,p＞0.05), SAP(12.72±1.73Kpa vs12.56±0.75Kpa,p＞0.05),LVDP(2.49±2.14Kpa vs3.13±1.74Kpa,p＞0.05),LVEDP(3.46±1.75Kpa vs4.28±1.81Kpa,p＞0.05)in ADR+G-CSF group showed decreasing tendency and LV+dp/dt(552.29±351.05Kpa/s vs423.00±297.63Kpa/s,p＞0.05)and LV-dp/dt[(-310.68)±266.66Kpa/s vs(-186.39)±264.32Kpa/s,p＞0.05]showed increasing tendency compared with ADR group.Meanwhile,the ADR+G-CSF group showed significant improvement in inhibition of cardiomyocyte apoptosis compared with ADR group (8.54±0.84%vs9.73±1.31%,p＜0.05),as well as histological analysis.Myocardium fibrosis and cardiomyocyte necrosis were weakened by G-CSF.And immunohestochemical analysis showed there were both CD133~+ cells in ADR and ADR+G-CSF groups.Conclusion:Our results suggest that administration of G-CSF improve cardiac function in vivo in ADR-induced myocardium injury in rats.The mechanism may be inhibition of cardiomyocyte apoptosis and recruitment of BMSCs auto-mobilized by G-CSF resulting regeneration of myocardium.