Effects Of DNR On The Expression Of Brain Natriuretic Peptide Gene In Cultured Rat Myocardial Cells And Brain Natriuretic Peptide In Diagnosingcardiomyopathy Induced By Daunorubicin

This studies were composed of three parts and were desined to investgate the effects of DNR on the expression of Brain Natriuretic Peptide in cultured rat myocardial cell,animal model and clinical tests.Part 1 Effects of DNR on the Expression of Brain Natriuretic Peptide Gene in Cultured Rat Myocardial CellsObjective:To investigate the effect of daunorubicin(DNR) on the gene expression of brain natriuretic peptide (BNP) in rat myocardial cells.Methods:Neona -tal WISTAR rat myocardial cells were cultured and were divided into three groups,including control group,DNR group(DNR 0.2mg/L) and DNR+ fructose-1, 6- diphosphate (FDP )group(DNR 0.2mg/L,FDP2mg/ml).The viability of myocardial cells and the expression of BNP gene were examined by MTT,RT-PCR and WESTERN BLOT.Results:The Viability of myocardial cells precipitous decreased with the increasing of concentrations of DNR. The expression and the synthesis of BNP decreased after receving DNR and no increasing were observed after receving FDP to inter-vene.Conclusions:DNR suppressed the expression of BNP gene in cultured rat myocardial cells and FDP couldn't reverse the suppressing effect.Part 2 Investigation to the Brain Natriuretic Peptide Content of Myocardium in Rats Induced by DaunorubicinObjective:To explore the value of brain natriuretic peptide (BNP) in diagnosing the myocardial induced by daunorubicin(DNR) by investigate the changes of the BNP level in myocardium tissue of the rat after administrating the DNR. Methods:Thirty-two male young wistar rats were randomly divided into two groups(n=16 in each).The first group served as control group(0.9%saline 1.0ml/kg q.3d×6).The other group received DNR (2.0mg/kg q.3d×6) by tail vein injection. The content of serum LDH,CK and myocardium tissue malondialdehyde (MDA) were measured by colorimetric method and at the time the level of myocardium tissue BNP were analyzed by s-p immunohistochemistry and WESTERN-BLOT after administrating the drug.Results:The levels of MDA and BNP in myocardium tissue increase (P <0.001)and no significant change were observed in the serum LDH and CK(P >0.05) after administrating DNR in experiment group. On the other hand there is no significant change in control group. Furthermore,the levels of BNP was higher in experiment group than in control group after receving DNR and saline respectively.Conclusions:BNP is a good indicator of DNR-induced myocardial.Part 3The changes and the clinical values of plasma brain natriuretic peptide concentration in children with acute leukemia accepted the chemotherapy of daunorubicinObjective:This study was performed to explore the clinical values of the brain natriuretic peptide(BNP) in evaluating the cardiotoxicity caused by daunorubicin( DNR )by studying the changes of the plasma BNP level of children with acute leukemia that accepted the chemotherapy with DNR.Methods:31 children with acute lymphoblastic leukemia were performed the induction chemotherapy in DVLP project. We measured the plasma level of BNP by enzyme linked immunosorbent assay( ELISA) at the beginning and completing of administrating DNR. Simultaneously, electrocardiography (ECG )and cardiac muscle enzymes(LDH1,CPK-MB) were measured as a rule.Results:The plasma level of BNP increased from (3.97±2.41/)ng/L to(18.25±7.63)ng/L(p <0.001). However, routing EKG and cardiac muscle enzymes(LDH1 CPK-MB) remained normal.Conclusions:The plasma level of BNP was more sensitive in early evaluating the heart function during the chemotherapy of DNR.