Renal protective effect of fenofibrate on rats with adriamycin-induced nephrotic syndrome and the underlying mechanism
Objective To observe the effects of fenofibrate on blood lipid,renal function and morphology,oxidative stress,inflammation and coagulation factors in rats with adriamycin-induced nephropathy,and to explore the renal protective effect of fenofibrate and its mechanism.Methods Thirty male Sprague Dawley(SD)rats were randomly divided into normal control group,model group and treatment group.Adriamycin 4 mg/kg and 2 mg/kg were injected into the tail vein on the first day and the seventh day of the experiment,respectively,thus creating the nephrotic syndrome rat model.Rats in the normal control group were injected with the same amount of normal saline through the tail vein.After 8 weeks of modeling,rats in the treatment group were intragastrically administered with fenofibrate(60 mg/kg)aqueous solution,and those in the remaining groups were intragastrically administered with an equal volume of normal saline.The general state,diet,urine volume and body weight of rats in each group were observed.The 24-hour urine of rats was collected and the 24-hour urine protein was detected by Coomassie brilliant blue method.At the end of the experiment,renal tissue and blood samples were taken.Pathological changes of renal tissue were observed by hematoxylin and eosin(H&E)staining.Serum creatinine(CRE),blood urea nitrogen(BUN),cholesterol(TC)and triglyceride(TG)were measured by a biochemical analyzer.Malondialdehyde(MDA),glutathione peroxidase(GSH PX),superoxide dismutase(SOD)and catalase(CAT)levels in renal tissue homogenate were detected by commercial kits.Serum C-reactive protein(CRP)and plasma fibrinogen(FG)were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with those of the normal control group,rats in the model group had a poor general state,gradual weight loss,significantly increased 24-hour urine protein,CRE,BUN,TC and TG,and abnormal morphologies of glomerules and renal tubules,suggesting the successful modeling of nephrotic syndrome.Fenofibrate could significantly alleviate the renal pathological changes in rats with nephrotic syndrome.The body weight of rats in the treatment group was generally higher than that in the model group in the same period.At the 8th week,there was a significant difference in the body weight between the model group and treatment group(P＜0.01).The level of 24-hour urinary protein was significantly lower in the treatment group than that of the model group in the same period,and it was more significant at the end of the 8th week(P＜0.01).Serum CRE,BUN,TC and TG at the end of the 8th week were significantly lower in the treatment group than those of model group(P＜0.05).Compared with those of the model group,rats in the treatment group had significantly lower MDA content in the renal tissue,higher activities of GSH-Px and SOD,lower serum CRP and lower plasma FG than those of model group(P＜0.05 or P＜0.01).Conclusion Fenofibrate may play a renal protective role in rats with adriamycin-induced nephropathy by reducing blood lipids and the expression levels of oxidative stress factors,inflammatory factors and coagulation factors.
NETL
NSTL
万方数据
