Korean Journal of Nephrology 1991;10(4):492-504.

백서에서 Puromycin Aminonucleoside 유발 국소성 분절성 사구체 경화증에 미치는 Lovastatin의 효과

김문재 , 최인준

Abstract

Hyperlipidemia in patients with nephrotic syndrome have long been recognized. The significance of the lipid abnormalities and its potential role in the progression of renal disease have all been a cause of debate. However, recent experimental and clinical studies have indicated that hypercholesterolemia may be an independent risk factor in the pathogenesis of of focal segmental glomer- ulosclerosis (FSGS) as it is in atherosclerosis. This study was undertaken to investigate the possible relationship between hyperlipidemia and development of glomerulos- celerosis by pharmacological intervention with lipid- lowering agent lovastatin (LVST) and by Microfil per- fusion into renal microvessels. The nephrotic syndrome was induced in uninephrectomized Wistar rats by chronic administration of puromycin aminonucleoside (PAN) and protamine sulfate (PS). Serial changes of urinary protein were measured at 14-day interval up to the 56th day; blood chemistry and renal histology were obtained at 28th and 56th day. Microfil perfusions were performed in rats of each experimental group at final sacrifice. The results are as follows: 1) Repeated injections of PAN and PS induced ne- phrotic syndrome with massive proteinuria and sus- tained hyperlipidemia, and light microscopic study of kidney demonstrated progressive FSGS with tubulointerstitial changes in short period. 2) The LVST-treated rats had significantly lower cholesterol and triglyceride, and lower BUN and creatinine than those in the simple PAN-treated group at each periods. Both groups of rats developed equiva- lent degrees of proteinuria and hypoalbuminemia. 3) Segmental glomerulosclerosis was induced and showed a significant increase in the PAN-treated group. However, segmental glomerulosclerosis was significant- ly prevented in the LVST-treated rats. 4) Microvascular pattern in Microfil perfusion showed more smoothly tapered and branching of preg- lomerular arteriole and nicely filled glomeruli in the control group, but there were irregular and beaded appearances in the preglomeular arterioles and multiple filling defects in glomeruli in the PAN-Treated group. In the LVST-treated group, those preglomerular changes and segmental glomerular filling defects were significantly suppressed when compared with those in the PAN-treated group. In conclusion, combined PAN and PS-induced segmen- tal glomerulosclerosis could be ameliorated on his- tologic and microvascular changes by reduction of hyperlipidemia with lovastatin. This suggests hyper- lipidemia contributes to the pathogensis of FSGS.