Experimental Study On Activation Of Nuclear Factor-kappa B In Adriamycin Induced Cardiomyopathy In Rats And Intervention Of Melatonin

Objective :TO explore the activation and effects of nuclear factor- kappa B(NF-B) in Adriamycin induced in rats so as to provide experimental and theoretical evidences for studying the mechanism of Adriamycin induced cardiomyopathy and for preventing and treating Adriamycin induced cardiomyopathy.Methods:30 male Sprague-Dawley(SD) rats were randomly divided into 3 groups of 10 animals each: Control group;Adriamycin(ADR) group;Adriamycin(ADR) plus Melatonin(MT) group. ADR was given at a dose of 2.5mg/kg/day by intraperitoneal injection(i.p) for every two days, from day 2 of the experiment and up to a cumulative dose of 15mg/kg.Melatonin was administered at a dose of 6mg/kg/day for every day and up to a maximal cumulative dose of 90 mg/kg, and starting 1day before ADR .when the tow drugs were given in combination ,MT was given 3 hours before each ADR injection. In control group ,instead of ADR and MT, the same volume of physiology saline was injected .Batches of 3 rats were killed 5 weeks after the beginning of administration of ADR, the tissue sample were taken from the left ventricle wall. The sample was stained with hematoxylin and eosin(HE) and examined with a light microscope; the contents of nitric oxide(NO) and the activity of inducible nitric oxide synthase(iNOS)in cardiac tissues were examined by spectrophotography; the change of the activation of NF-KB in myocardial cell were observed by immunohistochemistry method; The apoptosis information of myocardial cell was detected by TUNEL staining method of immunohistochemistry. All the date were analyzed using the software SAS6.12.Result:1,A semiquantitative study disclosed significance of difference in activity of NF-κB between the Control and the ADR group(p<0.05), MT can inhibit the activation of NF-κB(p<0.05);Furthermore ,there was no difference in activity of the NF-κB between the Control and the ADR+MT group(p>0.05). 2,A quantitative study disclosed significance of difference in the contents of NO and the activity of iNOS between the Control and the ADR group(p<0.05);MT can decrease the contents of NO and the activity of iNOS, there was significant difference between ADR group and ADR+MT group(p<0.05);there was significant difference between Control and ADR+MT group(p<0.05).3,A semiquantitative study disclosed Myocardial cell apoptosis in ADR group were significantly increased compared with that in Control group(p<0.05);MT can decrease myocardial cell apoptosis ,myocardial cell apoptosis in ADR+MT group were lower than that in ADR group(p<0.05); there were significant difference between Control and ADR+MT group(p<0.05).4,Correlation analysis: there was a significant positive correlation between activation of NF-κB and the activity of iNOS; and there was also a significant positive correlation between activation of NF-κB and the myocardial cell apoptotic index(AI%).Conclusion:1,ADR may induced the high activation of NF-κB and increased the contents of NO and the activity of iNOS ;ADR may induced myocardial cell apoptosis.2,The activation of NF-κB seemed to play a important role in Adriamycin induced cardiomyopathy, NF-κB seem to increase the activity of iNOS ,then significantly increased the content of NO in cardiac muscle and induced excessive oxidative stress; NF-κB possibly enhance myocardial cell apoptosis in Adriamycin induced cardiomyopathy.3,MT may inhibit the activation of NF-κB, and prevent excessive oxidative stress and suppress myocardial cell apoptosis, MT has protective effect in Adriamycin induced cardiomyopathy.