半月体タイプ抗GBM腎炎におけるtissue inhibitor of matrix metalloproteinase (TIMP) 過剰発現に対するアクテオサイド (TJC-160) の効果

抄録

In order to clarify the antinephritic mechanisms of TJC-160, we investigated the effect on the increased expression of TIMP in glomeruli of crescentic-type anti-GBM nephritic rats. We administered TJC-160 (30mg/kg/day, p.o.) to the rats from the 20th day to the 35th day after anti-GBM nephritis induction. TJC-160 suppressed proteinuria and total/fibrous crescent formation in glomeruli. TJC-160 suppressed the increased expression of TIMP in crescent, compared to vehicle injected control nephritic rats. In addition, TJC-160 inhibited the decreased activities of metalloproteinase (MMP) -1 and 2, 9 in glomeruli. Despite the inhibition of the decreased MMP activities, TJC-160 did not enhance the MMP activities in normal glomeruli in the in vitro study. TJC-160 had no effect on the activity of MMP in trypsin treated glomeruli of nephritic rats at the 25th and the 35th days.
These data show that the effect of TJC-160 to inhibit the process of fibrous crescent formation in anti-GBM nephritic rats may be partly due to the ability of TJC-160 to prevent TIMP expression in nephritic glomeruli.