ABSTRACT
To determine thrombin activation and fibrin deposition in the development of lupus nephritis in MRL lpr/lpr mice and the inhibitory effects of "shenle". "Shenle" (4g/(kg?d) orally) was administered daily to MRL lpr/lpr mice at the age of 8 weeks. After treatment for 20 weeks, we compared thrombin receptor (Protease Activated Receptor-1, PAR-1) expression with immunohistochemistry and fibrin deposition with MSB(Martius-Scarlet-Blue)staining in renal sections. PAR-1 mRNA expression was analyzed with RT-PCR method in the two groups. With the development of murine lupus nephritis, we observed an increase in thrombin receptor mRNA and severe fibrin deposition in renal tissue in the control group, while thrombin receptor protein expression was strikingly downregulated, suggesting its continuous activation and degradation. "Shenle" inhibited PAR-1 activation significantly and it was correlated with reduced fibrin deposition. These results suggested that thrombin activation may play an important role in the development of glomerulonephritis in MRL-lpr mice. "Shenle" ameliorated the murine renal lesions probably by inhibiting thrombin receptor activation and fibrin deposition.
ABSTRACT
To determine whether increased expressions of gelatinase A(MMP-2) and gelatinase B(MMP-9) occur in vivo in autoimmune MRL/lpr mice model and to investigate the modulation effects of "shenle." Shenle (4g?kg -1 ?d -1 ,orally) or methylprednisolone(MPS,25mg?kg -1 ?d -1 ,ip)was administered daily to MRL/lpr mice at the age of 8 weeks. The activities of MMP-2/9 by gelatin zymography were compared in kidney protein extracts and urine. After treatment for 20 weeks, a progressive reduction in positive proteinuria number/total mice (40% vs.33 3% vs.80%, proteinuria over 300 mg/dl as positive) and an elevated survival rate (70% vs.80% vs. 50%) were found in "shenle" and MPS groups compared with the control group. Histological analysis of kidney tissues indicated that both "shenle" and MPS could inhibit the mesangial proliferation and renal sclerosis. Using SDS-PAGE gelatin zymography, we have identified increased expressions of both latent and activated form enzymes of MMP-2/9 in urine and kidney extraction. Immunohistochemical staining showed both MMP-2 and MMP-9 were obviously up-regulated within glomerulus in control group. "Shenle" as well as MPS suppressed the expression of both latent and activated form of MMP-2/9. These in vivo results suggested that MMP-2/9 expressions might play an important role in murine lupus nephritis. "Shenle" delayed the development of glomerulonephritis and improved survival in MRL/lpr mice probably by suppressing the expressions and activities of MMP-2/9.
ABSTRACT
To explore expressions of ? smooth muscle actin (? SMA), plasminogen activator inhibitor 1 (PAI 1), matrix metalloproteinase 9 (MMP 9)and tissue type inhibitor of metalloproteinase 1 (TIMP 1) in renal vessels of 38 patients with immunoglobulin A nephropathy (IgAN), immunohistochemistry method was used to detect abundances of the above proteins. The results showed that ? SMA staining was found mainly in vascular smooth muscle cells (SMCs); apparent PAI 1 staining was also shown by vascular SMCs; MMP 9 expressed considerably in vascular both SMCs and endothelial cells; TIMP 1 was located only in vascular endothelial cells. In renal tissues of IgAN patients at Lee IV V grade, vascular expressions of ? SMA?PAI 1 and MMP 9 were significantly higher than those at Lee I III grade ( P