Significance Of The Expression Of CD4~+CD25~+T Regulatory Cells In Adriamycin-Induced Dilated Cardiomyopathy Rats

Objective The purpose of this study is to explore the effect of immunolesion in the pathogenesis and progression of dilated cardiomyopathy (DCM) by investigating the changes of CD4+CD25+T regulatoy cells and CD4+CD25+Foxp3+T regulatory cells (Treg) in peripheral blood mononuclear cells(PBMC)from adriamycin-induced dilated cardiomyopathy rats.Methods 50 healthy male SD rats were randomly divided into control group (CN, n=15) and adriamycin-induced dilated cardiomyopathy model group (DCM, n=35). The DCM group was administered adriamycin intraperitoneally at a cose of 2.5mg/kg, twice a week for 6 weeks. while the control group received an equivalent volume of 0.9% Sodium Chloride Injection alone intrap(?)itoneally. At 0 week,3rd week and 8th week, two groups were phlebo(?)omized from femoral vein. PBMC were obtained and stained by mono(?)one fluorescent antibody, then the alone or combined expression of CD25 and FoxP3 in CD4+T lymphocytes were examined by flow cytometry (FCM). While echocardiographic measurements such as left ventricular internal diameter at end-diastole (LVIDd), left ventricular internal dimension systole (LVIDs) and left ventricular ejection fraction (LVEF) were obtained at 0 week and 8th week. At last, fresh hearts were removed when the survival rats were killed and myocardial tissue sections were obtained and stained with Van-Gieson (VG) to analyz the histopathology change.Results 1) Echocardiographic measurements revealed that LVIDd, LVIDs of DCM group were enlarged and LVEF of DCM group were decreased compared with control group, and there were statistically significant (P＜0.01). The myocardial tissue sections presented that cadiocytes were hypertrophy, intercellular substance were swelling and widening, and myocardial fibrosis formned obviously than that of the control group.2) At 3rd week, peripheral frequencies of CD4+CD25+Treg and CD4+CD25+Foxp3+Treg were significantly decreased in DCM group compared with those in control group [(6.97±1.13)% vs (8.49±1.50)%, P=0.027; (4.82±0.78)% vs (6.61±0.99)%, P=0.001)].3) At 8th week, peripheral frequencies of CD4+CD25+Treg,CD4+CD25+Foxp3+Treg were significantly decreased in DCM group [(6.95±1.37)% vs (8.32±1.46)% in control group, P=0.013], [(4.76±0.82)% vs (6.617±0.991)%, P=0.000].Conclusion 1) The rat models of adriamycin-induced dilated cardiomyopathy were established.2) The frequencies of CD4+CD25+Treg were significantly lower in DCM group at 3rd week. At 8th week when the rat models were established, the frequencies of those also decreased significantly. This alteration may led the function of inhibit-autoimmune down and the immune homeostasis disbalance, which brought about immune responses to myocardial antigens and autoimmunity cadiocyte injury. That may be assiociated with the pathogenesis and process of dilated cardiomyopathy.