| Objective:To observe the effect of prednisone on the blood and urine biochemical markers, renal pathological changes,the expression of glomerular podocyte proteins nephrin and podocalyxin in adriamycin (ADR)-induced nephrosis (ADN) rats. To investigate the role of podocyte injury in the occurrence and development of ADN and the protective effect of prednisone on podocyte.Methods:24healthy male Wistar rats were randomly divided into three groups: control group (n=8), ADN group (n=8) and prednisone-treated group (n=8).Rat model of ADN was constructed with caudal-venous injection of ADR with the dose of4mg/kg.then3.5mg/kg after7days.At the4th week of the experiment, prednisone-treated group was treated prednisone at dose of12.5mg/kg per day.24-hours’ urinary protein(24hUP).urine creatinine and serum total protein(Tp).albumin(Alb).cholesterol (Cho), blood urea nitrogen(Bun). serum creatinine(Scr).were measured serially at the0,4th,8th week,and the values of creatinine clearance rate(Ccr) were calculated.At the end of the8th week.all rats were sacrificed to collect kidney tissues for microscopy observation of renal pathological changes.Extracellular matrix/glomerular area ratio (ECM/GA) and renal pathology points were determined.The expression of nephrin and podocalyxin in renal tissue were detected by immunohistochemistry method.and the mean absorbance value was measured by Image Analysis Software.Spss18.0statistical software was used for statistical analysis.Results:1.Changes of various biochemical index:At the4th week.compared with control group.24hUP.Cho and Scr of ADN group and prednisone-treated group were significantly raised.while Tp.Alb and Ccr were significantly reduced.A successful ADR nephrosis model was regarded.At the8th week.compared with ADN group.24hUP.Cho and Scr in prednisone-treated group were significantly reduced.while Tp.Alb and Ccr were significantly raised.Compared with the prednisone-treated group at the4th week,24hUP.Cho and Scr were significantly decreased.Tp and Alb were significantly increased. 2.Changes of renal pathology:The structure of glomerulus and renal tubules in control group was approximately normal.Glomerular hypertrophy,mesangial cells and mesangial matrix severe proliferation, protein cast and infiltration of inflammatory cells in tubulointerstitium can be seen in ADN group.The degree of pathological changes in prednisone-treated group was lighter than in ADN group. Compared with ADN group, ECM/GA and renal pathological points in prednisone-treated group were significantly decreased(all P<0.01).3.Compared with control group.nephrin and podocalyxin staining presented a lighter tan discontinuous short linear-like or punctiform pattern along the capillary loops of glomerulus in ADN group(both P<0.01). Compared with ADN group, prednisone-treated group ameliorated abnormal expression of them(both P<0.01).4.The expression of nephrin in ADN group was negatively correlated with24hUP, Cho, ECM/GA and glomerular pathology point(r=-0.864,-0.861.-0.909,-0.922respectively.all P<0.01).and positively correlated with Alb and the expression of podocalyxin(r=0.964.0.948respectively.both P<0.01).The expression of podocalyxin was negatively correlated with24hUP. Cho. ECM/GA and glomerular pathology point (r=-0.801,-0.792.-0.813,-0.821respectively,all P<0.01),and positively correlated with Alb(r=0.918. P<0.01).Conclusions:1.The rat model of ADN constructed with duplicate injection ADR is successful.2.Podocyte injury are closely related to the occurrence and development of proteinuria and the progress of renal pathological damage in ADN.Nephrin and podocalyxin can be used as a relatively sensitive index of podocyte injury in ADN.Decreasing of the expression of nephrin and podocalyxin may play an important role in the evolution processes of pathological changes of ADN.3.Prednisone can alleviate proteinuria and renal pathological damage of rats in ADN. The mechanism of it may be related to the upregulation of the expression of nephrin and podocalvxin. |
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