The Comparison Of The Effects Of Different Medicines On The Mobilization Of EPCs And The Observation Of The Therapeutic Effects Of Curing Acute Myocardial Infarction

Objectives:1.To evaluate the effects of Pravastatin and Granulocyto-colony stimulating factor(G-CSF)on the mobilization of Endothelial Progenitor Cells(EPCs) in the mice with Isoprenine induced myocardial infarction,thus to explore the proper dose,medicine and time of mobilization.2.To compare the two methods of making myocardial infarction model in rats with different ventilation methods and establish an economic and efficient model to improve survival rates and evaluate the cardiac function3.To investigate the effects of EPCs mobilization with Granulocyto-colony stimulating factor(G-CSF)on neovascularization,and evaluate the therapeutic effects with ultrasonic examination,hitologic staining and cardiac function.4.To observe the effects of propofol and midazolam on the releasing of VEGF (Vascular endothelial growth factor),and evaluate the intervention effects of them on the mobilization of EPCs induced by G-CSF.Methods:1.Myocardial infarction was induced in mice with Isoprenine,and then divided into four groups:control group,myocardial infarction group,Pravastatin group and G-CSF group.The above medicines were continuously injected for 5days,and the number of CD34~+MNC and EPCs was surveyed and the plasma concentration of VEGF was measured on the first,fifth,seventh and ninth day.2.The rat model of myocardial infarction was induced by left anterior-descending coronary artery ligation,in different respiratory controlling methods.The control group was the same as above without ligating coronary artery.Hemodynamic parameters including heart rates,left ventricular end-diastolic pressure and+dP/dt were observed and the cardiac function was assessd with langendorff at 4th week.3.Thirty six adult male rats were devided randomly into G-CSF treated group (30μg/kg/d),control group(saline)and myocardial infarction group(saline). G-CSF or saline was administrated subcutaneously for 5 days.the number of CD34~+MNC and EPCs was surveyed and the plasma concentration of VEGF was measured on the seventh day.Hemodynamic data was collected after the final echocardiographic assessment.4.Thirty six rat models of myocardial infarction treated by G-CSF for 5 days were devided randomly into three groups:G-CSF group,midazolam group and propofol group,saline,midazolam and propofol were continuously infused for 6h on the seventh day,and then the the number of CD34~+MNC and EPCs was surveyed and the plasma concentration of VEGF was measured.The mRNA expression of VEGF and Flk-1 was detected by RT-PCR.Results:1.The curves of mobilization of the medicines to EPCs varied as following:The normal control group had a low level base line,myocardial infarction group and Pravastatin group kept a higher level,but the G-CSF group had the highest level line.Both the number of EPCs and the concentration of VEGF had the highest value at the time point of the seventh day.The effects of G-CSF on the mobilization of EPCs correlates with the concention of VEGF positively. 2.At the 4th week,HR and absolute value of±dP/dt were higher in the two model groups than in the control group(p＜0.05),but the difference in the two model groups was not significant(p＞0.05).The myocardial infarction was induced successfully and was justified by histologic and morphmetric measurement3.G-CSF mobilization increased the number of circulating CD34~+MNC and EPCs.Compared to the baseline level on day lafter MI,heart function in G-CSF treated group was improved,whereas that in control MI group was deteriorated significantly 4 weeks after MI.Mobilization with G-CSF increased the serum level of VEGF on day 7 after operation and the vessel density at the scar and border region in G-CSF treated group and MI group.4.Midazolam increased the concentration of VEGF and promoted the mobilization of EPCs induced by G-CSF.,augmented the vessel density at the scar and border region and improved the cardial function,but propofol had none but the effect of improving the cardial function.Conclusions:1.Both Pravastatin and G-CSF could mobilize EPCs from bone marrow into peripheral blood,augment the concention of VEGF in myocardial tissue and in peripheral blood,but G-CSF has better effects than Pravastatin.The effects of G-CSF on the mobilization of EPCs2.Both the two respiratory controlling methods can be used in making the rat model of myocardial infarction.The survival rates can be improved through proper measures taken during and after the operation.3.In rats with myocardial infarction,the ventricular remodeling was attenuated, heart function improved,neovascularization promoted after EPCs mobilization with G-CSF applied in post infarction period,So EPCs mobilization with G-CSF is a promising novel therpy for myocardial infarction. 4.Midazolam can promote the mRNA expression of VEGF and Flk-1,increase the number of EPCs in the peripheral blood mobilized by G-CSF,and improve the cardiac function in the rats with myocardial infarction treated with G-CSF.