Prostaglandin E <sub> 1 </ Sub> Delay The Renal Injury Of Rats With Adriamycin Nephrosis,

Objective Adriamycin nephrosis model shows resemblance to two kinds of human glomerualr diseases, one is minimal change disease, the other is focal segmental glomerular sclerosis. It is known that proteinuria play an important role in the progress of nephropathy and is also associated with injury of podocyte. Nephrin particularly expressed by podocyte plays an essential role in not only the slit diaphram structure , but also mediating cell signaling. Glomerular sclerosis and renal interstitial fibrosis contribute to chronic renal failure. As a key fibrogenic cytokine, Connective tissue growth factor(CTGF) is involved in the pathogenesis of renal interstitial fibrosis. More and more evidence provided by clinical practice that PGE₁ can reduce proteinuria and protect renal function. To investigate the therapeutic effect of lipo-prostaglandinE₁ (prostaglandin E₁ in corporated in lipid microspheres, Lipo-PGE₁) on the adriamycin nephropathy rats and its possible mechanism, the expression of nephrin in MCD model rat kidney and the expression of CTGF in FSGS model rat kidney were detected in the experiment.Methods 1. Twenty two SD rats weighting 150 to 170g were divided into control group (n=6), experiment group(n=8) and Lipo-PGE₁ treating group(n=8). Rats received a single tail-vein injection of adriamycin(7.5mg·kg^-1) in experiment group and Lipo-PGEi treating group. At the same time, 0.9% saline in equal amounts in control group. Lipo-PGEi was given by i.v. at 20μg·kg^-1·d^-1 every dayfrom the 14th to 28th days in Lipo-PGE₁ treating group. Urine was collected using metabolic cages at day 0,14, and 28. Three group rats were killed at day 29. Renal speciments were removed through a flank incision under amobarbital anesthesia for inspecting expression of nephrin.2. Twenty four SD rats weighting 180 to 200g were divided into 3 groups at random: adriamycin nephropathy group(n=8), Lipo-PGEi treated group (n=8) and normal control group (n=8). The adriamycin nephropathy model was induced by adriamycin i.v. at 7.5mg·kg^-1 from vena caudalis . Lipo-PGEi was given by i.v. at 20μg·kg^-1·d^-1 from the 8th to 10th weeks. The renal pathologic changes of the rats were observed under light microscopy. The expression of connective tissue growth factor(CTGF) were analyzed by immunohistochemistry and western blot. Results 1. In adriamycin nephrosis MCD model , a nephrotic syndrome characterized proteinuria and hypoalbuminemia. Proteinuria reached maximum after 14 to 28 days. At day 28 , Proteinuria in Lipo-PGE₁ treated group represented marked decrease comparing to that in normal control group(p<0.01), meantime no prominent changes were observed in serum creatinine. Expression of nephrin protein in glomeruli in experiment group were lower than nomal control group(p<0.01). Expression of nephrin protein in glomeruli in Lipo-PGE₁ treated group were higher than experiment group (p<0.05).2. Lipo-PGEi significantly inhibited the progress of glomerular sclerosis and ameliorated the glomerular histopathological changes . Expression of CTGFprotein in both glomeruli and renal tubules interstitium in adriamycin nephrosis FSGS model group were higher than that in control group (p<0.01) . Expression of CTGF protein in both glomerulars and tubles interstitium in Lipo-PGE₁ treated group were lower than adriamycin nephrosis FSGS model group(p<0.05). Conclusions Lipo-PGE₁ can mitigate proteinuria in adriamycin nephrosis MCD rat model , which may be related to up regulating expression of nephrin. It can protect podocyte from more injure. Lipo-PGEi may inhibits the progression of impairment of adriamycin nephrosis FSGS rat model by reducing glomerular sclerosis and renal interstitial fibrosis, which may be related to the down regulating expression of CTGF. It may be an effective agent for the treatment of glomerulonephropathy.