Protective Effects Of Paecilomyces Hepiali On Adriamycin Nephropathy In Rats

Objective:In this study,we established adriamycin-induced nephropathy rat model to investigate the protecting effect of Paecilomyces hepiali on the kidney,observed the change of the kidney histopathology and the composition of the extracellular matrix,and the relationship of the renal fibrosis and the content of renal TGF-β1 TIMP-1,PAI-1 and OPN mRNAs.At last we discussed the protection of Paecilomyces hepiali in preventing and treating renal fibrosis,and we hope it may be a foundation for clinic using.Methods:Male SD rats(n=40) were randomized to four groups. Normal group (group N),n=10;Model group (group M),n=10; Paecilomyces hepiali group (group J), n=10; Benazepril group (group B), n=10. We establish chronic renal failure model with uninephreectomy with intravenous injeetion of adriamycin twice. After the first injection the rats in group J were administered orally by Paecilomyces hepiali 500mg/kg/d, the rats in group B by benazepril 4mg/kg/d, giving tap water of the equal volume to the rats in groups N and M.At the 8 weeks,we observed the 24-hour urine protein,lipids,plasma total protein (TP),serum albumin (ALB),blood urea nitrogen (BUN) and creatinine(Cr)levels.Renal pathology changes were evaluated at the 8th week with light and electron microscope.Immunohischemistry was used to examine the expression of OPN,FN, COL-IV in glomeruli; RT-PCR was used to examine the expression of TGF-β1 TIMP-1,PAI-1 and OPN mRNA at the 8th week after operation.Results:(1) group M compare with group N,24-hour urinary protein,BUN,creatinine, triglyceride(TG),total cholesterol (Cho) increased significantly (P<0.01),serum total protein and albumin decreased significantly (P<0.01).Compared with group M,the therapy groups(group B and J) can obviously improve serum total protein,reduce blood fat and urine protein, improve renal function.(2) Kidney morphology:In group M,we can see mild to moderate glomerular mesangial cell proliferation,expanded mesangial matrix and interstitial fibrosis with inflammatory cells infiltration.There was focal glomerulosclerosis and protein cast was obvious.In groups B and J, the medicine improve the above-mentioned histological changes.There was no such changes in group N.(3) Immunohistochemical techique can be seen in groups B and J, expression of osteopontin,collagenⅣand fibronectin was significantly lower than group M.(4) RT-PCR indicated that the expression of TGF-β1 TIMP-1,PAI-1 and OPN mRNA in group B and J is lower than group M.Conclusion:Paecilomyces hepialid can significantly reduce urinary protein lower blood urea nitrogen and creatinine, improve hypoalbuminemia, induc regulation of lipid metabolism disorders.The expression of osteopontin,collagenⅣand fibronectin which is ECM components in renal has decreased after treatment. Paecilomyces hepiali has a definite protective effect on renal fibrosis of the rat models.