The Effect Of TWP On The Podocytes Of Diabetic Nephropathyrats

Background and objective Diabetic nephropathy is an serious complication of diabetes mellitus and the major cause of end-stage renal diseases.its high incidence of poor efficacy.Podocyte injury is an important factor in the occurance and development of diabetic nephropathy, podocyte slit diagrame associated protein play an important role in the maintntance of glomerular filtration barrier integrity of the structure and function.Proteinuaria is not only a cardinal manifestation of renal dysfunction.The recent study evidences demonstrated that expressions of nephrin and podocin protein declined with proteinuaria increased. Tripterygium wilfordii polyglycosidium (TWP)was the traditional Chinese herbal medicine in our country .it has been used in variety of autoimmune diseases because its immunologic suppression function.In the present study ,we investigate the effect of tripterygium wilfordii polyglycosidium (TWP) on the change of pathomorphology in nephrin tissues , ultrastructure of podocytes ,expressions of nephrin and podocin protein and its mechanism in the kidney from diabetic rats.METHODS A rat model of DN was established. All rats were randomly divided into the normal control group(Group A),diabetic nephropathy control group (Group B) and TWP group(Group C). TWP group was devided into 3 subgroups (Ca, Cb, Cc) according to the different doses 4, 8, 16 mg·kg-1·d-1, respectively. After 12 weeks, UAER, BUN, Scr, WBC, GLU, and KW/BW were determined. The renal pathological changes were evaluated by HE staining. The structural changes of podocytes were observed by TEM. The expressions of nephrin and podocin were evaluated by immunofluorescence staining. RESULTS (1)Compared to group A , SCR, BUN, GLU, KW/BW, and UAER were significant higher(P<0.05) in group B and group C. Whereas the elevated liver enzymes and the decreased WBC were presented in group Cc(3/20 examples;15%).; The protein expressions of nephrin and podocin in nephridial tissue was lower, and the significant differences of pathomorphology in glomerulus, tubules and podocytes were observed in group B and group C. (2) Compared to group B, KW/BW and UAER were lower in group C (P<0.01);the protein expressions of nephrin and podocin were higher in nephridial tissue; The pathomorphological improvements were exhibited in glomerulus, tubules and podocytes in group C, paralleled with the increase of TWP dose (P<0.05 or P<0.01) .CONCLUSION TWP may exert the protective effect on podocytes in diabetic nephropathy rats, dependent on the dose of TWP. The mechanisms may involve the up-regulative expressions of nephrin and podocin, and the improvement of podocyte lesions.