EFFECT OF SAIREI-TO ON IRREVERSIBLE GLOMERULAR SCLEROTIC LESIONS IN RATS

The effects of Sairei-to and its active components on a model of irrev ersible mesangial proliferative glomerulonephritis induced by injectin g monoclonal antibody (MoAb) 1-22-3 into uninephrectomized rats were e xamined. The significant suppressive effects of Sairei-to and its acti ve components on proteinuria were demonstrated on days 7, 14, 21 after MoAb 1-22-3 injection compared with phosphate-buffered saline (PBS)-t reated controls. On day 21, light microscopy revealed that the drugs r educed mesangial cell proliferation, mesangial matrix expansion (matri x score: 84.5 +/- 41.6 for Sairei-to, 76.1 +/- 31.9 for Syo-saiko-to, 66.7 +/- 46.3 for its three components us 162.4 +/- 26.1 for PBS, P<0. 005) and crescent formation (mean percentage: 2.25% for Sairei-to, 1.7 1% for Syo-saiko-to, 1.43% for its three components us 18.86% for PBS, P<0.005). The kidney weights of the groups given the drugs were signi ficantly lower than the PBS group value (1.03 +/- 0.08 g with Sairei-t o, 1.11 +/- 0.12 g with Syo-saiko-to, 1.06 +/- 0.12 g with its three c omponents us 1.39 +/- 0.20 g with PBS, P<0.01 or P<0.05). Immunofluore scence analysis revealed that the drugs suppressed the expression of t ransforming growth factor-beta (TGF-beta), alpha-smooth muscle actin ( alpha-SMA) and collagen type I in the glomeruli, and reduced the numbe rs of ED1-positive cells in the glomeruli and OX8-positive cells in th e glomeruli and in the tubular interstitium. The blood biochemistry re sults revealed significant differences between the total cholesterol l evels (70.0 +/- 5.9 mg/dL with Sairei-to, 66.0 +/- 6.4 mg/dL with Syo- saiko-to, 76.6 +/- 8.4 mg/dL with its three components us 104.3 +/- 26 .6 mg/dL with PBS, P<0.05). We conclude that Sairei-to and its active components have suppressive effects on proteinuria and mesangial matri x expansion in rats with irreversible renal sclerosis. Transforming gr owth factor-beta, collagen type I and alpha-SMA expression and infiltr ation by ED1- and OX8-positive cells were also suppressed by these dru g preparations.