| Object To investigate the role of macrophage and monocyte chemoattractant protein-1(MCP-l) in the pathogenesis of nephrotoxic serum glomerulonephritis and the effect of novel immunosuppressive agents, leflunomide and tacrolimus on nephrotoxic serum nephritis in rats. Methods The experiment was pulled out in three stages. In an initial experiment, anti-GBM antiserum was prepared by immunizing rabbits with rat renal cortex homogenate. Next, the appropriate dosis of anti-GBM antiserum for inducing nephrotoxic serum nephritis were searched out at several dosis: 0.5, 0.8, and 1.0ml/200g body weight (three rats each). Finally, the role of macrophages and MCP-1 in glomerular injury and control of the nephritogenic injury with leflunomide or tacrolimus were carried out in 40 rats. There were 10 rats in control group; the nephrotoxic serum nephritis was induced in by injection of rabbit anti-rat GBM antibody into tail veins in other 30 rats. Rats with nephrotoxic serum nephritis were randomly divided into three groups: pathological group, leflunomide-treated group (5mg.kg-1.d-1, by gavage), tacrolimus-treated group (lmg.kg-1.d-1, by gavage), 10 rats in each group. Leflunomide and FK506 were administered daily for 14 days from six hours after injection of the rabbit antiserum. Levels of 24-hour urinary protein, serum albumin, serum creatine and blood urea nitrogen were determined. All rats were sacrificed and kidney specimens were collected at the 14th day. Glomerular morphology was observed by light microscopy and immunohistochemistry was performed. Result (1) Rats injected with rabbit antiserum excretion heavy proteinuria (P<0.01),...
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