| Adriamycin is anthracycline antitumor drug,which plays an important role in clinical because of its wide antitumor spectrum,strong antitumor effect and obvious curative effect.Unfortunately it has side effects,which can cause hair loss,bone marrow suppression and cardiotoxicity.Especially the cardiotoxicity is progressive and irreversible,eventually inducing Dilation Cardiomyopathy.There are many different theories about cardiotoxicity of adriamycin,including oxygen free radicals disorder,cell apoptosis,mitochondrial damage and iron?calcium disorders.And theory of oxygen free radicals disorder gets the most supporters,but the antioxidant drugs,such as vitamin E and N-acetylcysteine can not get the ideal effect,indicating the complexity of the formation mechanism of adriamycin cardiomyopathy.IL-17 is a new type of inflammatory factors secreted by Th17 cells,In recent years a large number of studies have shown that IL-17 to participate in a variety of disease development at home and abroad,including a large number of cardiovascular diseases,such as viral myocarditis progressing to Dilation Cardiomyopathy,restoring after myocardial infarction,hypertension,atherosclerosis,etc.Also it found that in many studies,IL-17,TGF-beta 1 and MMPs commonly activate in the various organ fibrosis,but there are few IL-17 and related downstream proteins playing the role in adriamycin induced chronic DCM fibrosis.Purpose:DCM rats model was built by using different concentration of adriamycin,to explore the ideal modeling adriamycin concentration,at the same time by detecting related protein expression in rat serum and myocardial to probe into its pathogenesis.Methods: 180 g male SD rats were randomly divided into 4 groups.Model group was given intraperitoneal injection of different concentration adriamycin to establish DCM model,and the control group was given saline.Pathological changes of the myocardial tissue of DCM rats,brain natriuretic peptide and interleukin-17,myocardial tissue in IL-17,matrix metalloproteinases and transforming growth factor beta 1 expression were evaluated.Results: compared with control group,cardiac index of model group A increased obviously(P<0.05),otherwise cardiac index of moder group B and C reduced(P<0.05);Compared with model group A,cardiac index of model group B,C reduced(P<0.05);Cardiac index of model group B and C has no obviously difference(P>0.05).Compared with control group,serum BNP level of model group A increased,but there was no statistically significant difference(P>0.05);Compared with the control group and model group A,serum BNP level of model group B and C increased obviously,the difference was statistically significant(P < 0.05);the differences of Serum BNP between model group B and C have no statistical significance(P>0.05).Compared with the control group,the level of serum IL-17 of model group A,B,C increased,the differences were statistically significant(P<0.05);Serum levels of IL-17 of model B and C were significantly higher than model group A,the difference was statistically significant(P<0.05);Serum IL-17 differences between model group B and C has no statistical significance(P>0.05).Compared with the control group,collagen volume fraction of model group A,B,C increased,the difference was statistically significant(P<0.05);Compared with model group A,collagen volume fraction of model group B and C increased,the difference was statistically significant(P<0.05);Collagen volume fraction differences between model group B and C has no statistical significance(P>0.05).Compared with control group,expression of IL-17,MMP2 and TGF beta-1of model group A,B,C in the myocardium are enhanced,the differences were statistically significant(P<0.05);compared with model group A,expression of IL-17,MMP2 and TGF beta-1 of model B and C in the myocardial are enhanced,the differences were statistically significant(P<0.05);expression differences of IL-17,MMP2 and TGF beta-1 of Model group B and C in the myocardial have no statistical significance(P>0.05).Conclusion: Small doses and long course of intraperitoneal injection of adriamycin to build cardiomyopathy rats model characterized by high success rate,low mortality rate,good repeatability,can be used as an ideal way,but you need to achieve cumulative dose of adriamycin.The expression of IL-17,MMP2 and TGF beta-1 were henced in the DCM fibrosis induced by adriamycin,that is to say,inflammation may have participated in this process. |
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