Treatment of chronic dysfunction of transplantation kidney in rats —by tanshinone, lysimachiae combined with mycophenolate mofetil or cyclosporine alone

Abstract

Objective: To evaluate the relationship between chronic kidney dysfunction after transplantation and chronic vascular rejection (CVR), and to evaluate the efficacy and safety of Tanshinone (Tan) and Herba Lysimachiae (Lys) combined with Mycophenolate Mofetil (MMF) to fight against CVR, and to reduce the incidence of chronic dysfunction in rat renal transplantation model.Methods: Sixty-five male SD rats as donors and sixty-five male Wistar rats as recipients were used. The recipients were divided into five Groups, including Group A: Lys + Cyclosporine A (CsA), Group B: Tan+CsA, Group C: MMF+CsA, Group D: CsA, and Group E: normal saline. Kidney function and morphological changes were assessed at 2, 4, and 6 weeks after transplantation. All sections of renal grafts were stained with monoclonal antibodies (McAB),. including major histocompability complex class II (OX-6), lymphocyte function antigen-1 (CDllb/CD18), intercellular adhesive molecular-1 (IA29), CD8+ (OX-8), and proliferation cell nuclear antigen (PCNA) (5A10, IgGlk) were used. Results:The two control groups developed typical chronic rejection episodes, and the histologic feature indication of kidney chronic rejection includes loss of renal units and presence of an obliteration arteriopathy involving large renal arteries. These were associated with serum levels of BUN and SCr increased and different degrees of glomerulosclerosis. Their mean survival time was lower than that of other groups. By contrast, serum levels of cytokine in control groups was significantly increased when compared with group B and C (P 0.05) between group B and C.Conclusions: CVR may activate the risk of the factor responsible for the development of graft chronic dysfunction that causes slow, progressive destruction of the transplanted kidney. Tanshinone was extracted from Salvia miltiorrhiza and purified for use in medicine. Especially when Tanshinone combined with a low-dose of CsA, it may fight against the CVR by inhibiting cell infiltration, and improving microcirculation of the graft, and thus the incidence of CVR is reduced. It is suggested that Tanshinone can be applied to treat patients with chronic renal dysfunction when used in combination with a low-dose Cyclosporine.