Effects Of Granulocyte Colony Stimulating Factor (G-CSF) And Simvastatin On Improving Heart Function And Reducing The Infarct Size In Acute Myocardial Infarction Rats

ObjectiveTo evaluate the effects of G-CSF and Simvastatin on heart function and left ventricular remodeling in acute myocardial infarction rats. To explore the mechanism of G-CSF and Simvastatin.MethodsExperimental myocardial infarction was created by left coronary artery ligation in Sprangue-dawly rats. After 24 hours of the above procedure, surviving rats were randomly assigned to the following 4 groups: (1) MI group(n=31); (2) G-CSF group(n=34); (3) Simvastatin group(n=32); (4) G-CSF and Simvastatin group(n=34); the other randomly selected rats were sham-operated group(n=30). Then the rats in these five groups were redivided into five subgroups according to the course of intervention: 2d(n =6),4d(n =6),7d(n =6),14d(n =6) and 28d(n =7,10,8,10,6,)subgroups. By the end of each course the rats were killed, the echocardiography, hemodynamics index of rats and wet-to-dry ratio of the lungs were measured, Morphological characteristics were evaluated with HE, Sirus-red, the size of infarction were assessed or calculated respectively with compute-assisted image analysis system (Image-Pro Plus, Version:4.5). Immunohistochemistry staining was performed to lable CD34 ,Ⅷ-R Ag , VEGF, ED-1, MCP-1, ICAM-1. The apoptosis of cells were detected by in situ end labeling technique (TUNEL). The proliferation of myocardium were detected by Double staining( Ki67 and CTnI).Results1 LVIDd and LVEDP of treatment groups were lower than those of MI groups(P<0.01 or P<0.05, except 2d, 4d subgroups), but were higher than those of SO groups(P<0.01 ); LAWd, EF, LVSP and±dp/dt of treatment groups were higher than those of MI groups(P<0.01 or P<0.05, except 2d, 4d subgroups), but were lower than those of SO groups(P<0.01 ).2 The percentage of infarct size of 28d treatment subgroups were decresed than that of MI groups (P<0.05 ). The wet-to-dry ratio of the lungs of treatment groups were decresed than those of MI groups, (except 2d,4d subgroups , P<0.05), but were higher than those of SO groups(P<0.01 ).3 The percentage of CD34 positive cells of peripheral blood of MI groups were higher than that of SO groups (P<0.01, except 28d subgroups), The percentage of treatment groups were higher than those of MI groups(P<0.05, except 28d subgroups), The number of CD34 positive cells of treatment in infracted myocardium was higher than those of those of MI groups (P<0.01, except 28d subgroups).4 The capillary density and the integrated optical density (IOD) of VEGF of MI groups were higher than those of SO groups (P<0.01); the capillary density and IOD of VEGF of treatment groups was higher than those of MI groups (P<0.01).5 The number of Ki67 and CTnI double staining positive cells of MI groups were higher than those of SO groups(P<0.01or P<0.05),the number of positive cells of treatment groups were higher than those of MI groups(P<0.01), the number of positive cells of MI-GS groups were higher than those of MI-G and MI-S groups( P<0.01 or P<0.05); The apoptosis index of cells of treatment groups were decresed than those of MI groups (P<0.01), but were higher than those of SO groups(P<0.01), the index of MI-GS groups were decreased than those of MI-G and MI-S groups. (P<0.01).6 The IOD of ED1, MCP-1 and ICAM-1 in the infarcted myocardium of treatment groups were higher than those of MI groups (P<0.01 or P<0.05), but were higher than those of SO groups (P <0.01), the IOD of MI-GS groups were decreased than those of MI-G and MI-S groups. (P<0.01 or P<0.05).Conclusions1 G-CSF and Simvastatin not only promote stem cells mobilizing and capillary neogenesising , but also reduce inflammation, promote myocardium proliferating and inhibit myocardium apoptosising.2 Comobination of G-CSF and Simvastatin, the effects of above-mentioned were reinforced, improve heart function better,inhibit ventricular remodeling and reduce the infarct size of left ventrical.