观察调素（OPN）在大鼠实验性新月体肾炎肾脏组织中的表达及功能性抑制OPN的活性对巨噬细胞在肾脏局部浸润的影响。方法 OPN在肾脏组织蛋白和基因水平的表达分别应用免疫组化双标记及原位杂交技术。结果 在实验性新月体肾炎肾脏织织内OPN的表达明显升高，并与肾脏局部巨噬细胞的浸润、肾脏病理损害程度及肾功能的下降明显相关。应用抗OPN抗体治疗以后可显著抑制OPN在肾脏组织的表达，同时巨噬细胞在肾脏组织的浸润也明显减少，肾脏病理损害减轻、肾功能明显改善。结论 OPN的高表达是实验性新月体肾炎发病过程中巨噬细胞在肾脏组织局部浸润的重要介导因子，抑制OPN的表达和功能可显著抑制肾脏局部巨噬细胞的聚集及改善肾功能。

Deexyspergualin (DSP) is a potent immunosuppressive drug which Inhibits acute renal allograft rejection and the development of experimental anti-GBM glomerulonephritis (GN). To investigate the mechanism by which DSP suppresses renal macrophage accumulation, we examined the effect of DSP treatment on osteopontin (OPN) expression, a monocyte chemotactic and adhesion molecule. Passive accelerated anti-GBM GN was induced in rats by priming with rabbit IgG, followed 5 days later by injection of rabbit-anti-GBM serum (day 0). Groups of five rats were treated with DSP (5mg/kg i.p. daily) or saline (untreated) from day 0 until being killed on days 1, 7, 14 or 21. Saline treated animals developed severe proteinuria and a loss of GFR. Antibody staining showed a marked pregulation of renal OPN expression which was associated with focal macrophage accumulation and renal damage, such as crescent formation and tubular lesions. DSP treatment significantly inhibited glomerular and tubulointerstitial OPN expression 75-85%, p<0.001). This was associated with a marked reduction in glomerular and interstitial macrophage accumulation (50% and 80%, respectively, p<0.001) and suppression of renal damage, including crescent formation (90%↓) and tubular atrophy. Ih conclusion, this study has identified that suppression of OPN expression is an importantmechanism by which DSP inhibits macrophage-mediated renal injury in experimental crescentic GN.

This stud yexamined whether osteopontin (OPN). A molecule with monocyte chemotactis andadhesive activity. Participates in macrophage-m,ediated renal idsease. Accelerated anti-glomerular basement membrane glomerulonephritis was induced in group of six rats. Animalswere treated with a neutralizinganti-OPN or an irrelevant control antibody over days 0-7 (inductionphase) or days 7-14 (established disease). administration of the control antibody had no effect on the severiy of thedisease. In contrast. anti-OPN treatment significantly reducedglomerular injury (urinary protein excretion) and preveted a loss of renal funciton (creatinine clearance) dring the inducion ofdisease. This was accompanied bya significant reduction in renal macrophage and T-cell accumulation. T-cell activaiton. and histologicalinjury (glomerular hypercellularity, segmental lesions. crescents. and tubulointerstitial lesions). An inportan finding was that anti-OPN treatment of established crescentic glomerulonephritis led to a significant reducion in golomerular injury and recovery of renal function in association withinhibition of macrophage and T-cell accumulation. T-cell activation. and histolgical damage. Anti-OPN treatment significantly inhibited the upregulation of OPN and its ligand CD44 but demonstrated no effect on upregulation of intercellular adhesion molecule-1 (ICAM-1) expressionin the kidney. Interestingly. anti-OPN treatment significantly reduced skin swklling and leckocyte infiltration in the delayed type hypersensitivityresponse. However, anti-OPN treatment hadno effect on the humoral immune response. In summary. this study has demonstrate that OPN plays a funcional role in macrophsage and T-cell accumulation and renal damage in both the inducionand progression of a rat model of crescentis glomerulonephritis. thus, OPN may be of pathologcal importance in human glomerulonehphrits and in cellmediated immune diseases generally.

目的 探讨CD44及其配体骨调素（OPN）在实验性新月体肾炎发展过程中的表达和作用。方法 应用兔抗鼠肾毒性血清制作新月体肾炎模型，免疫组化双标记及原位杂交技术检测CD44、OPN及其它指标。结果 CD44和OPN在新月体肾炎的发展过程中表达明显升高，并和巨噬细胞在肾脏组织的局部浸润、新月体的形成及肾功能的损害密切相关。结论 在实验性新月体肾炎模型，CD44和OPN在肾小球实质细胞和小管间质细胞显著表达，并可能在新月体肾炎的发病过程中发挥重要的作用。