Effects Of Prednisone On Interleukin-13 And Intercellular Adhesion Molecule-1 Expression Of Adriamycin-induced Nephropathy

Objective:To observe the effects of prednisone on the blood and urine biochemical markers, the expression of anti-inflammatory cytokine interleukin-13 (IL-13) and pro-inflammatory cytokine intercellular adhesion molecule-1 (ICAM-1) in adriamycin (ADR)-induced nephropathy (ADN) rats. And investigate the role of two factors in the development of nephritic syndrome.Methods:24 healthy male wistar rats were randomly divided into control group (n=8), ADN model group (n=8) and prednisone group (n=8). After 3 days adaptive feeding, ADN model group and prednisone group were initially injected adriamycin with the dose of 4 mg/kg, then 3.5 mg/kg after 7 days. While the normal control group received 9 g/L sodium chloride solution with the same volume at the same time. Prednisone group was treated at 4th week of the experiment for 4 weeks at dose of 12.5mg/kg. Water was administered respectively to the other groups by gavage at the same time. Serum index were measured serially at 0th,4th,8th weeks, including total protein (Tp), albumin (Alb), cholesterol (Cho), blood urea nitrogen (Bun), serum creatinine (Scr).24 hours urine protein and urine creatinine were measured simultaneously. The values of creatinine clearance (Ccr) were calculated. At the end of 8th week, rats were sacrificed to collect kidney tissue for microscopy observation after 40 g/L formaldehyde buffer formalin-fixed, paraffin-embedded, cut, line HE staining, PAS staining. Extracellular matrix/glomerular area ratio (ECM/GA) and renal pathology points were determined. The expressions of IL-13 and ICAM-1 in renal tissue were detected by immunohistochemistry-SP. Measured and calculated the mean absorbance value by Image-Pro Plus 6.0. Spss16.0 statistical software was used for statistical analysis.Results:1. The changes of various biochemical index:Compared with normal control group at 4th week,24hUP, Cho, Scr of ADN group and prednisone-treated group were significantly raised, Tp, Alb and Ccr significantly decreased, regarded as successful ADR nephropathy model. At 8th week,24hUP, Cho, Scr of ADN group continued to raise, Tp, Alb and Ccr decreased continually. There was a significant difference of Cho and Ccr compared with the first 4 weeks. Compared with ADN group at 8th week, 24hUP, Cho in the prednisone-treated group rats were significantly reduced, Tp, Alb and Ccr significantly raised. Compared with the prednisone group at 4th week,24hUP, Cho, Scr were significantly decreased, Tp, Alb were significantly increased. There was no significant difference of Ccr although higher than the level at 4th week.2. Pathological changes:Light microscopic observation result showed that:The control group had no significant pathological changes. Balloon adhesion, mesangial cells severe hyperplasia, basement membrane thickening, endothelial cell proliferation, vacuolar degeneration, and some tubulointerstitial lesions can be seen in ADN model group. The degree of pathological changes in prednisone group was lighter than in ADN model group. Compared with ADN group, ECM/GA and renal pathology points in the prednisone group rats were significantly reduced, the expression of IL-13 and ICAM-1 were significantly decreased. IL-13 and ICAM-1 level of kidney tissue in ADN group rats were positively correlated with 24 hours urine protein, cholesterol, ECM/GA and renal pathology points, and negatively correlated with albumin. IL-13 expression of glomerular in prednisone group was positively correlated with Cho, ECM/GA, glomerular pathological scores and ICAM-1 expression of glomerular, and negatively correlated with Tp and Alb. The expression of ICAM-1 is positively correlated with Cho, and negatively correlated with Tp, Alb.Conclusion:The rat model of ADN constructed with duplicate injection Adriamycin is successful-Imbalance of IL-13 and ICAM-1 might contribute to the pathogenesis of ADN and had associated with prognosis of the disease by regulating cytokine steady-state institution.The prednisone reduces the production of inflammatory factor ICAM-1, as well as the anti-inflammatory factor IL-13. Observe the expression of IL-13 and ICAM-1 may reflect the progression of NS and the effect of the treatments.