Effect Of Basic Fibroblast Growth Factor On Adriamycin Induced Oxidative Stress In Myocardium Of Rats

Objective:To study effetcs of basic fibroblast growth factor (bFGF) on adriamycin (ADM) induced oxidative stress in myocardium of rats.Methods:Fourty Wistar rats were randomly divided into five groups: control group, ADM group, ADM+bFGF (Ⅰ)group, ADM+bFGF (II) group, ADM+bFGF (Ⅲ) group. ADM, bFGF was dissolved in aseptic normal saline. Administration of ADM was the same volum(10.0ml-kg-1) intraperitoneal injetcion (ip), administration of bFGF was the same volumn (1.0 ml-kg-1) intramuscular injetcion (im). control group:first time ip and im aseptic normal saline 10.Oml-kg-1,1.0 ml-kg-1 one time, respetcively, after then im 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 im aseptic normal saline(1.0ml-kg-1) one time, after then im aseptic normal saline 1.0 ml-kg-1 each day one time in the two days.ADM+bFGF (I, II, III) three groups:administration of ADM dosage and method were the same as ADM group.administration of ADM while im bFGF(the dosage of bFGF in three groups were 800.0,1600.0,3200.0U·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 hydrogen sulfide (H2S), hydrogen peroxide (H2O2),hydroxyl radical (OH-),superoxide anion (O2.-), malondialdehyde(MDA) in myocardial tissues, and creatine kinase isoenzymic MB(CK-MB) in serum; enzyme-linked immunosorbnent assay method were used to determine the contents of metallothionein(MT) and nitrotyrosine (NT,a maker of peroxynitrite); the activity of cystathioniney-lyase (CSE) in myocardial tissues; The expression of MT1 mRNA,MT2 mRNA and CSE mRNA were detected by reverse transcription polymerase chain reaction (RT-PCR) method in myocardial tissues.Results:ADM group:the contents of MDA, H2O2,OH-,O2.- and 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 MT1 mRNA,MT2 mRNA,CSE mRNA and the activity of CSE, the contents of MT and H2S in myocardial tissues were significantly reduced than those in control group(P<0.01).ADM+bFGF(I,Ⅱ,111) three groups:the contents of MDA, H2O2,OH-,O2.- and 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 MT1 mRNA,MT2 mRNA and CSE mRNA, and the activities of CSE,and the contents of MT and H2S in myocardial tissues were significantly increased than those in ADM group(P<0.01),the changes were obviously dose-dependent with bFGF.Conclusion:bFGF inhibited the oxidative stress in myocardium induced by ADM. bFGF inhibited the oxidative stress in myocardium induced by ADM, this was related to bFGF antagonized the inhibitory effects of ADM on the expression of MT1 mRNA, MT2 mRNA and CSE mRNA in myocardial tissues,thereby antagonizes the inhibitory of ADM on the activities of CSE and MT syntesis, H2S production in myocardial tissues, thereby reduced the generation of O2.-,H2O2,OH·and peroxynitrite in myocardial tissues.