Effect Of Granulocyte Colony-Stimulating Factor On Adriamycin Induced Oxidative Stress In Myocardium Of Rats

Objective:To study effetcs of granulocyte colony-stimulating factor(G-CSF)on adriamycin(ADM)induced oxidative stress in myocardium of rats.Methods:Fourty Sprague-Dawley(SD) rats were randomly divided into five groups: control group, ADM group, ADM+G-CSF(Ⅰ) group ,ADM+G-CSF(Ⅱ) group, ADM+G-CSF(Ⅲ) group. ADM , G-CSF was dissolved in aseptic normal saline. Administration of ADM was the same volumn(10.0ml·kg-1)intraperioneal injetcion(ip), Administration of G-CSF was the same volumn (1.0 ml·kg-1 ) sucutaneous injetcion(sc). control group:first time ip and sc aseptic normal saline 10.0ml·kg-1, 1.0 ml·kg-1 one time, respetcively, after then sc aseptic normal saline 1.0 ml·kg-1 each day one time in the two days. ADM group: ip ADM(10.0mg·kg-1) one time, the same time sc aseptic normal saline(1.0ml·kg-1) one time, after then sc aseptic normal saline 1.0 ml·kg-1 each day one time in the two days.ADM+G-CSF ( I,II,III) three groups: Administration of ADM dosage and method were the same as ADM group. Administration of ADM while sc G-CSF (the dosage of G-CSF in three groups were 15.0,30.0,60.0μg·kg-1, respetcively) each day one time for three times. All animals were sacrificed at 72 hours after drug used. Spectrophotometric method were used to determine the contents of malondialdehyde(MDA) ,nitric oxide(NO) ,hydrogen peroxide (H2O2),hydroxyl radical(OH·), superoxide anion (O2.-),the activities of copper-zinc superoxide dismutase(Cu-Zn SOD) , manganese superoxide dismutase(Mn SOD),glutathione peroxidase(GPx), constitutive nitric oxide synthase(cNOS), inducible nitric oxide synthase(iNOS),creatine kinase isoenzymic MB(CK-MB) in serum; enzyme-linked immunosorbnent assay method were used to determine the contents of tumor necrosis factor-alpha (TNF-α) and nitrotyrosine (NT,a maker of peroxynitrite);The expression of Mn SOD mRNA,Cu-Zn SOD mRNA,GPx mRNA,iNOS mRNA and TNF-αmRNA were detected by reverse transcription polymerase chain reaction (RT-PCR) method.Results: ADM group: The expressive levels of iNOS mRNA and TNF-αmRNA,the activity of iNOS, the contents of MDA,NO,H2O2 ,OH·,O2.-,TNF-αand NT in myocardial tissues,the activity of CK-MB in serum were significantly increased than those in control group(P<0.01), the expressive levels of Mn SOD mRNA,Cu-Zn SOD mRNA,GPx mRNA and the activities of Mn SOD,Cu-Zn SOD,GPx in myocardial tissues were significantly reduced than those in control group(P<0.01), the activity of cNOS in myocardial tissue was not significant difference as control group(P>0.05). ADM +G-CSF(Ⅰ,Ⅱ,Ⅲ) three groups: The expressive levels of iNOS mRNA and TNF-αmRNA,the activity of iNOS,the contents of MDA , NO,H2O2 ,OH·, O2.- ,TNF-αand NT in myocardial tissues,the activity of CK-MB in serum were significantly reduced than those in ADM group(P<0.01), the expressive levels of Mn SOD mRNA,Cu-ZnSOD mRNA,GPx mRNA and the activities of Mn SOD,Cu-Zn SOD,GPx in myocardial tissues were significantly increased than those in ADM group(P<0.01), the activity of cNOS in myocardial tissue was not significant difference as ADM group(P>0.05).Conclusion: G-CSF inhibited the oxidative stress in myocardium induced by ADM. G-CSF inhibited the oxidative stress in myocardium induced by ADM, this was related to G-CSF antagonized the inhibitory effects of ADM on the expression of Cu-Zn SOD mRNA,Mn SOD mRNA, GPx mRNA in myocardial tissues,thereby antagonizes the inhibitory of ADM on the activities of Cu-Zn SOD,Mn SOD, GPx in myocardial tissues,and G-CSF inhibited the expression of iNOS mRNA in myocardial tissues reduced by ADM, and reduced the activity of iNOS, thereby reduced the generation of O2.-,H2O2 ,OH·and peroxynitrite in myocardial tissues.