EFFECTS OF " SHENLE" ON THE EXPRESSIONS AND ACTIVITIES OF GELATINASE A AND B IN AUTOIMMUNE MRL/lpr MICE / 解放军医学杂志

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.