| Objects and methodsHeart failure is a worldwide public health problem.It is the final endpoint of cardiovascular diseases and the main cause of death.With the development of aging population,the survival rate of acute cardiovascular events increases,as well as the increase of disease susceptibility(such as diabetes and obesity),the incidence and mortality of heart failure are increasing year by year.Major breakthroughs were made in the treatment of heart failure in recent years,the latest of the American college of cardiology(ACC/AHA)and the European society of cardiology(ESC)treatment guidelines recommend to treat falling heart patients with diuretics,angiotensin converting enzyme inhibitors(ACEI)and angiotensin receptor blockers(ARB)or beta blockers,mineralocorticoid receptor blockers which can reduce total mortality in patients with heart failure and can significantly improve the quality of survival in these patients.Additionally,mechanical interventions,such as resynchronization therapy,are beneficial to severely ill patients.However,heart failure is still an unsolved disease,one of the most common,costly,disabling and fatal diseases encountered by clinicians,and still needs further research.Heart failure is the final stage of development of many diseases,which is affected by many factors.For example,patients who receive anthracycline chemotherapy are at high risk of heart failure,and these patients often have heart failure in the middle and late stages of treatment.The anthracycline anticancer drug doxorubicin is an effective and frequently used chemotherapeutic agent for various malignancies.Its major adverse effect is cardiotoxicity,which may limit its use.Doxorubicin cardiomyopathy,once developed,carries a poor prognosis which is frequently fatal.However,the cardiac toxicity of doxorubicin is dose dependent,so that it is limited in clinical applications.Its characteristic cardiotoxicity is left ventricular dysfunction,which can eventually lead to congestive heart failure and dilated cardiomyopathy.Reducing the dose of doxorubicin can reduce the incidence of cardiac toxicity,but when the cumulative dose below 450 mg/m2,the body will appear abnormal function.In addition,none of the current strategies for primary prevention of doxorubicin cardiotoxicity have been routinely used,and new therapeutic strategies need to be developed.Colchicine is an inexpensive,oral,powerful anti-inflammatory drug that has been used as an anti-inflammatory to acute gouty arthritis for a long time until recently was considered as a second-line treatment for other cardiovascular diseases,such as acute pericarditis,atrial fibrillation and acute coronary syndromes.Its mechanism is to inhibit tubulin polymerization and microtubule formation,and prohibit the activities of cell adhesion molecules,inflammatory chemokines and inflammasomes,which affects the inflammatory levels.Recent studies have found that colchicine has clinical significance in the treatment of coronary heart disease atherosclerosis,and coronary atherosclerosis and heart failure have inflammatory pathogenesis hypothesis,based on this theory,thus,this study investigated the therapeutic effect of the anti-inflammatory drug colchicine on doxorubicin-induced heart failure hamsters,providing more clinical strategies for the treatment of heart failure.To illustrate the colchicine treatment for heart failure induced by doxorubicin hamster meaning and related mechanism of cardiovascular physiological changes.The physiological changes of cardiovascular disease in Syrian golden hamsters are very similar to those in humans,thus,we choose wild type Syrian golden hamsters,and intraperitoneal injection of doxorubicin to establish animal model of heart failure and feed these hamsters with colchicine treatment.Cardiac ultrasonography was performed at the 12th and 16th week to analyze the changes in the heart function of hamsters.The hamsters in the experimental group and the control group were sacrificed,and related tissue samples were obtained.The expression levels of ANP,BNP,TGF-?,apoptotic proteins LC3Band P62 were detected by qPCR and Western blot,and the differences between these groups were compared.ResultsSuccessfully established congestive heart failure model of hamster by intraperitoneal injection of doxorubicin,heart failure hamsters were given colchicine,and Cardiac ultrasonography was performed on the 12th and 16th weeks.we found that after colchicine treatment,heart failure hamsters have been relatively improved in left ventricular pump function and qPCR results which showed that the indexes of ANP,BNP,TGF-?gene expression levels.Western blot results showed that the expression of apoptotic proteins LC3B,P62 and the ratio of II/I decreased.ConclusionColchicine can reduce the doxorubicin-induced cardiotoxicity,the apoptosis of myocardial damage,the expression of apoptotic protein,and improve the cardiac pumping function of heart failure,suggesting that it has a certain therapeutic significance for congestive heart failure caused by doxorubicin.Colchicine can inhibit the expression of LC3B in the heart tissue of hamsters with DOX heart failure,thus inhibit the formation and polymerization of microtubules,promote the depolymerization of microtubules,reduce the load of cardiomyocytes,improve sarcomere movement and restore cardiac contractile pumping function... |
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