Continuous Changes Of The Immune System In Diabetic Rats And Effects Of Cyclosporine A On The Immune System

Objective:Diabetes mellitus(DM)is a metabolic syndrome characterized by hyperglycemia either due to an absolute deficiency in insulin secretion or to a reduction in the biologic effectiveness of insulin.The incidence of DM is rising in recent years.The long-term complications of diabetes mellitus,which affect the health of diabetic patients,can happen in all organs.Recently,studies showed that abnormal immune responses might contribute to diabetes and its long-term complications. Our previous studies demonstrated that the immunological complexes,deposited on the organs of the diabetic rats,decreased by the administration of cyclosporine A(CsA). Pancreas,kidney,retina,pituitary gland,aorta,sciatic nerve and cerebrum were included. In the present study,our investigation aimed at the continuous changes of the immune system in diabetic rats induced by streptozocin(STZ)and the effect of cyclosporine A on the immune system.To further investigate the immunologic mechanism of diabetes and its long-term complications,so as to provide theoretic basis for diabetic immunotherapy.Methods:One hundred and eight male rats(Sprague-Dawleys)were randomly divided into six groups,including normal control group(CON),diabetes group(DM), insulin treatment group(INS),low dose CsA group(CSL),medium dose CsA group (CSM)and large dose CsA group(CSH).The diabetic rats were established by intravenous injection of streptozocin(50mg/kg)through the caudal vein.The levels of blood glucose were tested respectively after 72 hours and 1 week post modeling.The diabetic models were qualified when both of the levels were higher than 16 mmol/l. Normal saline(0.1ml/d)was injected subcutaneously to CON and DM groups, isophane insulin(4-6IU/d)was injected subcutaneously to INS group,CSL,CSM and CSH groups were administered with CsA at doses of 0.5mg/kg.d,1mg/kg.d and 2mg/kg.d respectively.The rats sacrificed and the samples were harvested after 2,4 and 8 weeks post modleling.Blood glucose,weight,serum total protein,serum albumin and urine microalbumin 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 intestinal mucosa were evaluated by immunohistochemistry and immunofluorescence.Results:Excluding CON group,the blood glucose levels were higher than 16 mmol/l.Compared with CON group,markedly elevated blood glucose levels, significantly reduced weight,elevated urine microalbumin,decreased weight of the spleen and thymus,increased positive cells of IgA and IgG,increased CD4~+T and CD8~+T lymphocytes in the spleen,and increased CD4~+T lymphocytes and decreased CD8~+T lymphocytes in the intestinal mucosa were found in all the other groups. Compared with DM group,increased serum total protein and albumin,improved weights of spleen and thymus,decreased CD8~+T lymphocytes and IgA and IgG positive cells in the spleen,and increased CD8~+T lymphocytes in the intestinal mucosa were found in the Cyclosporin A treatment groups.Conclusions:The diabetic models might be successfully established by intravenous injection of streptozocin(50mg/kg)through the caudal vein.Atrophy of spleen,degeneration of thymus,as well as abnormal changes of lymphocyte number and ratio appeared in STZ-induced diabetic rats.The changes of T lymphocyte subgroups were not similar in the different tissues.The administration of CsA to STZ-induced diabetic rats might be beneficial to the hepar,alleviate spleen atrophy and thymus degeneration,as well as reduce abnormal changes of T lymphocyte subgroups in the spleen and intestinal mucosa.