The Prophylactic Effects Of Cyclosporine A On Cytoautoimmune Infiltration And Fibrosis To The Kidneysin The Streptozotocin-induced Diabetic Rat

Objective:Diabetic nephropathy is one of the most common chroniccomplicationsand the major cause of advanced renal fialure.It is commonly accepted for the timebeing that therapeutic principles for diabetic nephropathy are described asfollowing: control of hyperglycemia and hypertension and restriction of proteinintake as well as the protection of renal function.More and more evidence showedthat immunocytes was involved in pathogenesis of DN.In the current study, it isfound by pathology that the infiltrations of lymphocytes and macrophages in renaltissue have been shown that for the cyto-autoimmune injuries to kidneys in DN.Transforming growth factor-beta (TGF-β) signal pathway may play a critical role inthe pathogenesis of diabetic nephropathy(DN) through inducing cell hypertrophy ofglomerulus and renal tubule,accelerating the accumulation of extracellular mat rix(ECM),and promoting glomerulosclerosis and tubulointerstitial fibrosisOur aim was to investugate the mRNA expression of CC chemokines, cytokineTGF-β1 and in diabetic nephropathy induced by streptozotocin and infiltration oflymphocytes,infiltration of macrophage expression of MIP-1αand evaluated effect ofCsA on them.Method: The diabetic model of rat (Sprague-Dawleys) were established byintravenous injection of streptozotocin(50mg/kg) through the tail.then the diabetic ratswere randomly divided into 8 groups, DM, AMI,BML,BMM, BMH,AML,AMM,AMH groups,to which cyclosporineA were admini-strated at a variousdoses of 1mg/kg/d,4 mg/kg/d, and 8 mg/kg/d.eight weeks later infiltration oflymphocytes were investigated by light microscopy,infiltration of macrophage wereevaluated by immunohistochemistry.MIP-1A were detected by semi-quantitivereverse transcript-ploymerase chain reaction(RT-PCR)Result: The over-expression of MIP-1αand TGF-β1 were found in DMgroup. A significant infiltration of lymphocytes as well as macrophage and kidney fibrosis were detected in DM group, the over-expression,infiltration ofimmun ocytes and kidney fibresis were decline in CsA-intervented group.Conclusion:There were significant infiltration of immunocytes in kidney ofSTZ-induced diabetic rats with overexpression of MIP-1α. The infiltration oflyrnphocytes and rnacrophage,the expression of MIP-1αwere decline byadministration of CsA in STZ-induced diabetic rats.Then The over-expression ofTGF-β1 were found in STZ rats.Auto-immune injuries to the kidney in STZ-induced diabetic rats were detected at time of 8 weeks.It is by insulin injection that thefibrosis may be relieved at least in part while CsA treatment seems to have lessinjuries than that treated with insulin for the kidney protection.It is concludedthat the injuries to kidney could be prevented by the administration of CsA inSTZ-induced diabetic rats.