| Objective: through the establishment of diabetic nephropathy (DN) rat model to study the influence of leflunomide on the rat kidney PKC and MCP-1 and explore furtherly the leflunomide's role in the DN rat treatment and its mechanism.Methods: Divide 30 male Wistar rats randomly into three groups: comparison group, DN group and leflunomide group. Furtherly divide it into two groups according to different observation time (8 w, 12w), and each group is given five. Induced rats'renal with streptozotocin (STZ) to the DN model, after the molding in the leflunomide group and make the gavage leflunomide 5 mg / kg everyday. Give the same capacity saline to comparison group and DN group. Each fortnight- carry through one time measured blood glucose and body weight. At the end of the experimental section 8 w and 12w, respectively take five animals from the three groups, utilize the metabolism cages to collect urine for 24h urine test 24h urine volume and 24h urine protein; measuring cardiac blood creatinine (Scr), blood urea nitrogen (BUN); anatomy of the kidney removal kits membrane, weighing, renal tissue from doing HE staining and electron microscopy observation of renal tissue specimens pathological changes, detecte kidney MCP-1 protein expression with the method of immunohistochemistry, and check the RIA of renal tissue PKC activity.Results:(1) Model DN is only a minor mode, and its rate of mode was 95%. It can go on being experimented by the availability of DN model added to experiment. After the major model, there is no death and the mortality is 0%.(2) With the extension of the course, the kidney weight of the rats of DN group increases, and creatinine clearance rate increased, and there is proteinuria. Compared with the comparison group, there were significant differences (P <0.05). The urine protein, serum creatinine, urea nitrogen of the rats of Leflunomide group decreased compared with the same period DN group significantly, and there were significant differences (P <0.05).(3) From histopathology observation the thickening of glomerular basement membrane of leflunomide group reduced significantly, compared with DN group, and mesangial cell proliferation and extracellular matrix deposition reduced, that explain the leflunomide can reduce kidney damage.(4) In the renal tissue of comparison group, MCP-1 in glomerular and tubular expression of a small, DN group of MCP-1 expression was significantly enhanced, after the leflunomide treatment, in rat kidney MCP-1 expression was significantly reduced, meaning that leflunomide can reduce the MCP-1expression.(5) Compare the cytoplasm PKC activity of DN group and the comparison group in the same period, it decreased significantly, but the membrane PKC activity was significantly increased (P <0.05). Through the leflunomide treatment, compared with the DN group in the same period, the cytoplasm PKC activity increased, the membrane PKC activity decreased (P <0.05), indicating that leflunomide can inhibit the activation of PKC.Conclusion: Leflunomide can reduce the expression of MCP-1 and inhibit PKC activity, thereby to protect DN rat kidney.
|
PDF Full Text Request