The Study Of Mobilizing Autologus Bone Marrow Stem Cells By G-CSF And Using BFGF In Acute Myocardial Infarction

Recently, numerous studies confirmed that mobilizing stem cells homing to the infracted zone can engender new cardiac-like cells,which participate in the infracted myocardial restoration and improve the impaired cardiac fuction in actue myocardial infarction (AMI). Meanwhile, the studies also confirmed that the growth factor can improve the blood supply in the infarcted zone and the cardiac fuction by promoting angiogenesis in AMI. But the mechanisms of the specific role and the dosage,time,way of injiection for the two methods is still evolving, the more simple and effective way of making the two treatments synergy is not yet clear. This study observed the effects in promoting the cardiac fuction of rats after AMI contrastingly, by the way of mobilizing autologus bone marrow stem cells by granulocyte colony stimulating factor (rhG-CSF) alone, or using basic fibroblast growth factor (bFGF) alone, or in combination of the two together, in order to provide a theoretical basis and foundation for clinical applications in AMI. The experiment was set up by 5 groups:sham operated group (S),AMI group (MI),G-CSF group (G),bFGF group (B),Conbination group (GB). S group were never received ligation or drug;MI,G,B,GB group were induced AMI model by ligation of the left anterior descending artery, and were respectively injected intraperitoneally 24 hours after AMI with 0.9% NS (2ml/d),rhG-CSF (15ug/kg·d),bFGF (0.5ug/kg·d),rhG-CSF(15ug/kg·d) conbined with bFGF (0.5ug/kg·d), once per day for 7days. Respectively, counted the white blood cell (WBC),mononuclear cells (MNC) proportion in peripheral blood of each group 24 hours and 1 week after injection, tested their cardiac fuction in vivo, caculated the infarcted size of each group 4 weeks after AMI, and observed the pathological changes of cardiac and vascular regeneration of the specimens both 1w and 4w after AMI by hematoxylin and eosin (HE) staining and immunohistochemical staining under optical microscope variously. The data was dealed with statistical analysis. The results were as followed: 15 rats died during 4 weeks after AMI in sum (the mortality was 19.29%). The quatitities of WBC and the MNC proportion in peripheral blood 1w after AMI were larger than 24h after AMI in group MI,G,B,GB, while there were no obvious differences between that in group S. The comparision in the quatitities of WBC and the MNC proportion in peripheral blood of all groups displayed that GB>G>B>MI>S, but there were no obvious differences between that in group MI and S. The comparision of the density of capillary vessels both 1w and 4w after AMI revealed that GB>G or B>MI>S, but no significant differences were there in group G and B. The comparision of the infarcted rate 4w after AMI showed that GBGB>G>B>MI, and of LVDP is SG>B>MI>S. HE staining showed myocyte coagulative necrosis,inflammatory cells infiltration and fibrotic repairment. Immunohistological studies revealed that there were many CD34 positive cells in the infracted area of group G and group GB obviously 1w after AMI,particularly in group GB. The conclusions were as followed: Injecting rhG-CSF (15ug/kg·d) since 24h after AMI for 7 days intraperitoneally can mobilize bone marrow stem cells into peripheral blood in infarct rats. The mobilized stem cells may enter into the infarcted area and induce the regeneration of cardiac-like cells and capillary endothelial cells. It also improved the cardiac function significantly. Injecting bFGF (0.5ug/Kg·d) since 24h after AMI for 7 days intraperitoneally may also promote the regeneration of capillary in infarct area, but do not induce cardiac-like cells regeneration. It can improve the cardiac function, but the efficacy was less than that of rhG-CSF. Using rhG-CSF alone was more benefit than bFGF in reducing infracted size and improving cardiac fuction, but there're no obvious difference in promoting capillaries regeneration. bFGF participated in mobilizing stem cells by rhG-CSF, and coordinate with each other. The combination of rhG-CSF (15ug/Kg·d) with bFGF (0.5ug/Kg·d) would promote more cardiac-like cells and capillary regeneration, and improve the cardiac function more significantly than they were used alone.