Experimental Study of the Progressive Glomerulosclerosis Induced by Long-term Administration of Puromycin Aminonucleoside in Rats

Kim, Mi Kyung; Lee, Hyun Soon

Abstract

Pathogenetic mechanisms of progressive glomerulosclerosis are not clear. We studied the long-term(10 weeks) effects of puromycin aminonucleoside(PAN) in Sprague-Dawley rats with or without uninephrectomy(UN). Compared to rats with PAN injections only, rats with uninephrectomy and PAN injections showed significantly higher serum levels of urea nitrogen(153 +/- 155 mg/dl vs. 16 +/- 4 mg/dl, p<0.01), ceatinine(2.96 +/- 1.21 mg/dl vs. 0.92 +/- 0.36 mg/dl, p<0.01), cholesterol(466 +/- 125 mg/dl vs. 94 +/- 27 mg/dl, p<0.01), and triglyceride(337 +/- 237 mg/dl vs. 111 +/- 36 mg/dl, p<0.05) as well as increased amounts of proteinuria(428 +/- 90 mg/day vs. 136 +/- 130 mg/day, p<0.01). Lesions of focal segmental glomerulosclerosis(FSGS) were more frequently observed in rats with UN and PAN injections than rats with PAN infections only(39.5 +/- 17.2% vs. 4.3 +/- 4.7%, p<0.01). Ultrastructural examination of the glomeruli from rats with UN and PAN injections revealed severe epithelial cell changes including foot process effacement, vaculoar change or pseudocyst formation and focal detachment of epithelial cells from the underlying basement membrane. The results suggest that chronic nephrosis induced by PAN showed functional and morphologic features similar to those of human FSGS. Cytotoxic effect of PAN on the glomerular epithelial cells may be an initiating factor for the development of FSGS. which may be aggravated by some hemodynamic changes induced by uninephrectomy.