| Objective: Diabetes mellitus (DM) is commonly believed to be a metabolic syndrome characterized by hyperglycemia due to an absolute or relative deficiency in insulin secretion. The majority of DM patients undergoes a cascade of pathogenesis of the disease at the various periods of time in which many organs may be involved such as blood vessel, nervous system, muscular system, the skin and so on. The mechanism of these chronic complications still remains unclear while recent studies have implied that the autoimmune injuries and the biological effects of lymphokine could play an important role in the pathogenesis of chronic complications in DM. Our previous work has also demonstrated that the deposition of immunological complexes of several kinds, such as IgA, IgG, IgM, C1q, C3 and FRA, on the various organs, such as kidney, muscle, skin, and retina. Thus, it is very interesting to study if these chronic complications could be prevented by immunosuppressive agents, such as CsA. In the present study, Our aim mainly focuses on the abnormal deposition of immunoglobulins and expressions of several cytokines in the renal artery in STZ-induced diabetic rats and evaluated the protective effects of cyclosporine A.Materials and methods: Ninety rats were devided into nine groups while there were ten rats in each group. The diabetic rat models were given STZ(50mg/kg) intravenously. Then, they were randomly divided into three CsA-treated groups(DML, DMM and DMH, which were given CsA 0.5mg/kg·d, 1mg/kg·d and 2mg/kg·d respectively), one insulin-treated group(INS, insulin 2-6U/kg·d) and one diabetic group(DM, without any treatment). There were another three CsA-treated groups(NL, NM and NH) which were normal rats while were given CsA 0.5mg/kg·d, lmg/kg·d and 2mg/kg·d respectively. The control group(CON) had ten normal rats. Hepatic function, renal function, serum insulin and urine albumin were investigated every month. All rats were killed 16 weeks later. The deposition of immunoglobulins, nuclear factor-kappa B, monocyte chemotactic factor-1 and tumor necrosis factor-alpha were detected in the kidney artery by immunohistochemistry.Results: All rats treated with CsA had not shown any impairment on the hepatic and renal function. In the renal artery of STZ-induced diabetic rats, interstitial fibrosis was clearly demonstrated along with many monocytes infiltration and foam cells which were typical changes of atherosclerosis. Compared with controls, all diabetic rats had more deposition of IgA and IgG. Compared with DM group, the STZ-induced diabetic rats treated with CsA had less fibrosis and immunoglobulins. There was a significant positive correlation between the fibrosis and the deposition of immunoglobulins in the STZ-induced diabetic rats. All diabetic rats had more cytokines than the controls which were reduced by CsA.Conclusions: The presence of monocytes and foam cells in the renal artery of STZ-induced diabetic rats suggests that the autoimmune injuries play a critical role in the pathogenesis of the chronic diabetic macroangiopathy. Immunosuppressive treatment with CsA has demonstrated protective effects by inhibiting the abnormal deposition of immunoglobulins and the expression of the several cytokines in the STZ-induced diabetic rats. Our conclusions may challenge the traditional theories of the pathogenesis of atherosclerosis in diabetes.
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