Abstract
Severity of tubulointerstitial lesions, especially fibrosis has been proposed as one important risk factor on the prognosis of renal diseases. The purpose of this paper is to investigate the effectiveness of drugs such as both Angiotensin II type-1 receptor blockade (Olmesartan) and an immunosuppressant agent (Mycophenolate mof etil: MMF) on puromycin aminonucleoside and protamin nephropathy (PAPN) in a prototypical rat model of human focal segmental glomerulosclerosis associated with nephrotic syndrome and tubulointerstitial fibrosis. When the group of rats treated with both drugs were compared with a non-treated group on the 12th week after treatment, body weight and mean blood pressure in both groups were found to have no significant difference. The amount of proteinuria, the severity of both glomerulosclerosis and tubulointerstitial fibrosis, and the intensity of both hyaluronic acid (HA) and osteopontin (OPN) staining in the tubulointerstitial tissues (TIT) of the treated rats was significantly reduced : in contrast, the intensity of angiotensin II (Ang II) in the TIT was significantly increased. The relationship between percent occupancy of TIT fibrosis and factors, such as proteinuria, glomerulosclerosis, alf a smooth muscle actin HA and CD44 positive cells showed a positive correlation sohile Ang II and AT1 showed a negative correlation. These studies suggest that Olmesartan may reduce glomerular blood pressure and the severity of glomerular sclerosis : in addition, MMF may reduce the production of inflammatory factors such as OPN which contribute to the reduction of TIT and result in amelioration of PAPN.
