| Objective:To observe the resistance to prednisone and improvement of icariin on focal segmental glomerulosclerosis induced by adriamycin in rats,and to explore its possible mechanism.Methods:48 male Wistar rats of SPF grade were divided into control group(10 rats)and establishment group(38 rats)according to random number table method.The FSGS model was established by single tail vein injection of adriamycin 6.0 mg/kg,which was successfully established with urine protein > 100 mg/24 hours.Two rats were randomly selected to take renal histopathological examination as FSGS to verify the model.After successfully established,36 rats in establishment group were randomly divided into model group(10),prednisone group(10rats,given 6.3mg/kg.d),icariin group(8rats,given50mg/kg.d),prednisone combined with icariin group(8rats,given PDN 6.3mg/kg.d and Ica 50mg/kg.d).All rats were gavaged with different drugs for 6 weeks,of which the nomal and model groups were given water.Weighed rats body and collected 24-hour urine for protein quanti-fication every 2 weeks.At the end of the experiment,blood biochemical indicators were detected by automatic biochemical analyzer.Renal histopathological sections were made by HE staining and MASSON staining,and pathological changes were observed under micro-scope 200 times.Western blot technique was used to detect the expression of Nephrin and Podocin protein.Results:1.Compared with the control group,the weight,24-hour urinary protein,blood urea nitrogen,serum creatinine,cholesterol and triglyceride in the model group were significantly increased(P < 0.05),while total protein and albumin were decreased(P < 0.05),blood cortisol,glucocor-ticoid receptor-alpha and 17-hydroxycorticoid in the last urine were decreased(P <0.05).Pathological examination showed that glomerular sclerosis and shrinkage occurred,and protein tubules were found in some renal tubules.The expression of Nephrin and Podocin in renal tissue of model group decreased significantly(P < 0.05).2.Compared with model group,the difference of weight,24-hour urinary protein,blood urea nitrogen,serum creatinine,cholesterol and triglyceride was not statistically significant(P > 0.05),but total protein and albumin were more lower(P < 0.05),blood cortisol,glucoco-ticoid receptor-alpha and 17-hydroxycorticoid were more lower in the last urine(P < 0.05).The pathological changes of focal segmental glomerulosclerosis were not significantly alleviated.The difference of the expression of Nephrin and Podocin proteins in renal tissue was not statistically significant(P > 0.05).3.Compared with the model group,the difference of weight,24-hour urinary protein,blood urea nitrogen,serum creatinine,total protein and albumin in icariin group was not statistically significant(P > 0.05).The levels of cholesterol and triglyceride were lower(P <0.05),and the levels of blood cortisol were higher(P < 0.05).There was no significant difference between the model group and this group in the glucocorticoid receptor-alpha and the last urine 17-hydroxycorticosterol(P > 0.05).The pathological changes of focal segmental glomerulosclerosis were not significantly alleviated.The difference of the expression of Nephrin and Podocin proteins in renal tissue was not statistically significant(P > 0.05).4.Compared with the model group,the difference of weight,24-hour urinary protein,blood urea nitrogen,serum creatinine,cholesterol and triglyceride in the combination group of prednisone and icariin decreased significantly(P < 0.05),while total protein and albumin increased(P<0.05).Blood cortisol,glucocorticoid receptor-alpha and 17-hydroxycorticosterol were higher(P<0.05).The pathological changes of focal segmental glomerulosclerosis were significantly alleviated.The expression of Nephrin and Podocin in renal tissue increased significantly(P<0.05).Conclusion:1.The rat model of focal segmental glomerulosclerosis induced by adriamycin isinsensitive to prednisone treatment and can be used as a model of steroid resistant nephroticsyndrome.2.Icariin can alleviate the prednisone resistance of adriamycin-induced focal segmental glomerulosclerosis.Its mechanism may be related to the protection of podocytes by up-regulating podocyte marker proteins Nephrin and Podocin,which further confirms that Wenyang method has a sensitizing effect on hormones. |
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