The Effects Of Pioglitazone On Changes Of Spleen And Thymus In Diabetic Rats

Objective:In the recent years,the incidence of diabetes mellitus has risen.The long-term complications of diabetes mellitus,which cause the patients suffer greatly, can occur in all organs.Studies show that abnormal immune reactions might contribute to diabetes and to it's long-term complications.Previous studies also demonstrated that immunological complexes could be found on many organs of diabetic rats.T1DM is an autoimmune disorder,people with genetic predisposition can be stricken by it under certain circumstance.Some researcher have presumed that the essence of T2DM is a mild chronic systemic inflammatory state,abnormal immune reaction can cause insulin resistence,the apoptosis ofβcells and long-term complications.Pioglitazone,as a kind of insulin sensitization agent of thiazolidinediones(TZDs),is used to treat diabetes,recent research showes that TZDs have the effect of immunological regulation.Our research aimed at the change of spleen and thymus in diabetic rats provoked by streptozin(STZ) and the effect of pioglitazone upon it,to further investigate the immunologic mechanism of diabetes and it's complications,so as to provide theoretic basis for diabetic immunotherapy.Methods:Ninety six rats were randomly divided into eight groups:low dose pioglitazone group(PioL);high dose pioglitazone group(PioH);insulin and low dose pioglitazone group(INS+PioL);cyclosporine A group(CSA);insulin and cyclosporine A group(INS+CSA);insulin group(INS);diabetes group(DM);normal control group(CON).Diabetic rats were established by intravenous injection of streptozocin (45mg/kg) through the caudal vein,blood glucose were tested after 72 hours and 1 week post modeling,the diabetic models were qualified when both of the blood glucose were higher than 16.0 mmol/L.PioL group and PioH group were administrated with pioglitazone(4,20mg/kg·d) intragastriclly respectively.Isophane insulin(2U/kg·d) and pioglitazone(4mg/kg·d) were given to INS+PioL group subcutaneously and intragastrically.Cyclosporine A(1mg/kg·d) was administrated to CSA group subcutaneously.Isophane insulin(2U/kg·d) and cyclosporin A(1mg/kg·d) were given to INS+CSA group subcutaneously.Isophane insulin(2U/kgd) was injected subcutaneously to INS group.No treatment was given to DM and CON groups.After 16 weeks post modleling,the rats were put to death and the samples were harvested.Blood gucose,serum insulin,weight,renal function and hepatic function were evaluated.The weight of spleen and thymus was recorded.CD4~+ T lymphocytes,CD8~+ T lymphocytes,as well as IgA,IgG and IgM positive cells in the spleen and tymus were evaluated by immunohistochemistry.Immunoglobulin were detected by immumofluorescence method.By specific stain,the number of macrophages and the amont of fibrin in the spleen were evaluated.Results:After STZ infusion,the rats' blood glucose levels were higher than 16.0 mmol/L,they were successfully induced into the diabetic models.Elvated creatine, urea,nitrogen,urine protein,triglyceride,as well as decreased insulin,albumin, globulin and total protein were confirmed in diabetic rats.While only slight changes happened in PioL group and PioH group.Atrophy of spleen,degeneration of thymus, decreased weight of both spleen and thymus were found,as well as increased lymphocyte,decreased ratio between CD4~+ and CD8~+ T lymphocytes,increased imunoglobulin G and M.The number of macorphages and the amount of fibrin in spleen were elevated in diabetic rats.The weight of spleen and thymus in PioL group and PioH group was higher than that of CON group.Decreased imunoglobulin G and M,increased lymphotes and increased ratio between CD4~+ and CD8~+ T lymphocytes were also found in in PioL group and PioH group.Conclusions:Diabetic models might be successfully established by intravenous injection of STZ,through the caudal vein.Atrophy of spleen,degeneration of thymus, changes of lymphcyte subgroups,as well as deposition of immunoglobulin could appeared in STZ-induced diabetic rats.Pioglitazone might be beneficial to the hepetic and renal function.Pioglitazone could alleviate spleen atrophy and thymus degeneration,reduce the abnormal changes of T lymphocyte subgroups,as well as lessen deposition of immunoglobulin in the spleen and thymus.