| Summary: | 碩士 === 臺北醫學大學 === 醫學技術學系 === 95 === Anti-thy1 antibody-induced glomerular nephritis is a well established animal model for Mesangial cell proliferative glomeruli nephritis. Dipyridamole is a phosphodiesterase inhibitor, which has been shown to reduce GN-associated proteinurea. However, the detail mechanisms by which dipyridamole exert its therapeutic effects has not been elucidated. In the present study, we investigate the effect of dipyridamole on anti-thy1 -induced glomerular nephritis. We found that injection of anti-thy1 antibody resulted in acute glomerular nephritis (GN), characterized with massive proteinurea, increased of ED(+) macrophage infiltration and moderate PCNA(+) cell proliferation. These effects were all inhibited by treatment of rats with dipyridamole (5mg/Kg). TGF-βhas been shown to play an important role in extracellular matrix secretion. We next examined whether treatment of dipyridamole exerted beneficial effects on glomerular TGF-β expression and extracellular matrix accumulation. Injection of anti-thy1 antibody resulted in a mild increase of glomerular TGF-β and extracellular matrix accumulation as revealed by increased PAS score. Treatment of GN rats with dipyridamole significantly reduced the PAS score and TGF-β expresseion levels in glomeruli. Thy-1 antibody induced the expression of hem-oxygenase-1 (HO-1), a stress-induced marker, and the HO-1 induction was inhibited by treatment of rats with dipyridamole. Osteopontin, a bone sialoprotein, has been linked to renal fibrosis. I next investigate whether osteopontin (OPN) plays a role in anti Thy1 Ab-induced GN. OPN was constitutively expressed in tubules, Bowman’s capsule, and glomerular tuft of normal kidney. Injection of anti-thy1 antibody increased OPN expression in renal tubules but not in glomeruli, suggesting OPN was not associated with thy1-induced GN and subsequent renal fibrosis. Treatment of cells with dipyridamole reduced thy1-antibody stimulated OPN expression in renal tubule, but has little effect on glomerular OPN expression. Taken together, our results demonstrated that dipyridamole exhibited beneficial effects on thy-1 antibody induced GN.
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