The Effects And Mechanism Of Granulocyte Colony-stimulation Factor(G-CSF) In Mice With Heart Failure By Angiotonin Ⅱ

Aim: To certify:1 The effects and feasibility of G-CSF in chronic heart failure;2.There is up-regulation of G-CSFR in failing heart;3. The mechanism of G-CSF's effects in cardiomyocyte maybe associated with the expression of G-CSF receptor (G-CSFR) and osteoponin.Methods: 27 6-weeks-aged black-skin C57BL/6 male WT mice were randomized into 3 groups(n=9):1.control group;2.heart failure group: imbedded the osmotic minipump which is full of angiotonin II, its administrating speed designed about 2ug/Kg/min ,keep on 4weeks;3 .G-CSF group (treatment group): imbedded the osmotic minipump which is full of angiotonin II, its administrating speed designed about 2ug/Kg/min ,keep on 4weeks,and start the treatment on the day imbedded the osmotic minipump,the detailed treatment: peritoneal injected the rhG-CSF with 10ug/Kg/d,designed the course of treatment as 5days injecting and 2days interval,carried out 4courses.On the day 28,measured the left ventricle end-diastole diameter(LVEDD) left ventricle end-systolic diameter(LVESD) and ejection fraction(EF) with echocardiograph, recorded the blood pressure heart rate and body weight,then killed the mice to obtain their hearts,weigh the heart and the left ventricle,divided the left ventricle to 2 sections: one section stored in Formalin, paraffin imbedding, slice, then giving HE stain and Masson's trichrome stain, investigating the levels of apoptosis and fibrosis in heart muscular tissues, and measuring the width of cardiomyocyes and the proportion of the area of fibrosis cardiomyocytes; the other section stored with liquid nitrogen,abstracting the proteinum to investigate the expression of G-CSFR and osteoponin with RT-PCR.Results:1.The blood pressure heart rate heart weight/body weight and left ventrivleweight/body weight of heart failure group are significantly higher than control group(p<0.01) ;2. The blood pressure heart rate heart weight/body weight and leftventrivle weight/body weight of treatment group versus heart failure group decreasedsignificantly (p<0.01) ;3. The width of cardiomyocyes and the proportion of the area of fibrosis cardiomyocytes in heart failure group increased significantly,versus control group (p<0.01) ;4. The width of cardiomyocyes and the proportion of the area of fibrosis cardiomyocytes in treatment group decreased significantly,versus heart failure group (p<0.01 ) ;5.The LVEDD and LVESD in heart failure group increased,the EF decreased significantly,versus control group (p<0.01) ;6. The LVEDD and LVESD in treatment group decreased o,the EF increased significantly,versus heart failue group(p <0.01) ;7.The expression of G-CSFR in heart failure group is significantly higher than control group (p<0.01) ;8.The expression of G-CSFR has no significant difference in heart failure group and treatment group;9.The expression of osteoponin in control group and treatment group is lower significantly than heart failue group (p<0.01)Conclusions: 1..G-CSF is good for heart failue treatment,it can improve even prevent the fibrosis in cardiomyocytes,protect the heart function;2. There is up-regulation of G-CSFR in failing heart, and has no obviously change post-treatment;3.The effects of G-CSF in heart failure treatment is associated with the expression of G-CSFR in heart;4.G-CSF can prevent the fibrosis in cardiomycytes through the decrease of osteoponin's expression in heart.