OBJECTIVETo examine the effect of multi-glycoside of Tripterygium wilfordii Hook. f. (GTW) on proteinuria and expression of slit diaphragm-associated molecules such as nephrin and podocin in glomerulonephritis induced by anti-Thy1.1 antibody (anti-Thy1 . 1 GN).

METHODSAnti-Thy1.1 GN was induced in rats by a single intravenous injection with 500 microg of anti-Thy1.1 mAb 1-22-3. Fourteen rats were randomly divided into 2 groups, the GTW-treated group and vehicle treated group, and sacrificed on day 14 in Experiment 1 or on day 7 in Experiment 2 after induction of Anti-Thy1.1 GN. Daily oral administration of GTW and vehicle as a control was started from 3 days before injection or at the same time of injection to the day of sacrifice in Experiment 1 or 2. Proteinuria was determined during 14 days in Experiment 1 or during 7 days in Experiment 2. From kidneys taken at sacrifice, glomerular morphological changes, glomerular macrophage infiltration, glomerular expression of nephrin and podocin, and its mRNA expression in renal tissue were examined.

RESULTSIn Experiment 1, proteinuria and mesangial matrix expansion were significantly attenuated by GTW treatment. No difference in staining intensity of nephrin and podocin in glomeruli was observed between GTW treated group and vehicle treated group on day 14. In Experiment 2, GTW treatment significantly ameliorated proteinuria, mesangial injury and activated macrophage infiltration in glomerulus. In addition, it significantly increased the expression of nephrin and podocin and its mRNA expression in glomeruli on day 7.

CONCLUSIONIn anti-Thy1.1 GN, the reduced expression of nephrin and podocin may contribute to the development of mesangial injury and proteinuria. The findings suggest that GTW ameliorates not only proteinuria but also mesangial lesions in anti-Thy1 . 1 GN most likely by increasing the expression of nephrin and podocin.