摘要目的观察激素及环磷酰胺静脉冲击治疗对新月体肾炎(CGN)患者肾小球单核细胞趋化蛋白-1(MCP-1)、巨噬细胞炎性蛋白-1α和β (MIP-1α、MIP-1β)以及CD68表达的影响,进一步阐明其治疗CGN的机制.方法选择激素及环磷酰胺静脉冲击治疗1至3个月后进行重复肾活检的CGN患者12例,其中狼疮性肾炎(LN-CGN)和血管炎(V-CGN)患者各6例.应用免疫组织化学方法检测肾小球MCP-1、MIP-1α、MIP-1β和CD68的表达.结果虽然激素及环磷酰胺静脉冲击治疗能够明显减少CGN患者肾小球新月体数,其对狼疮肾炎和血管炎肾小球中趋化因子表达的影响明显不同.LN-CGN患者细胞性新月体的肾小球中CD68、MCP-1和MIP-1α的表达均较治疗前明显减少, 有显著性差异,MIP-1β的表达也较治疗前有所下降,但无显著性差异;V-CGN患者细胞性新月体的肾小球中CD68较治疗前明显下降,有显著性差异,而MCP-1、MIP-1α和MIP-1β较治疗前有所下降,但无显著性差异.重复肾活检时,V-CGN肾小球硬化及小管间质纤维化程度明显高于LN-CGN.结论激素及环磷酰胺静脉冲击对LN-CGN和V-CGN的治疗反应不同,可能与肾小球MCP-1、MIP-1α和MIP-1β变化的差异有一定的关系.

abstractsObjective To study glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α and β (MIP-1α, MIP-1β) and the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on expression in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment.Methods Twelve patients with initial biopsy-proven CGN2, 6 with lupus nephritis (lupus-CGN, LN-CGN) and 6 with vasculitis, (vasculitis-CGN, V-CGN) were enrolled in this study. They underwent an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and were biopsied again one to three months later. Expression of MCP-1, MIP-1α, MIP-1β, and CD68 in glomeruli with cellular and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies. The effect of the pulse therapy on histopathological changes was also observed. Results Although steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescent formation both in LN-CGN and V-CGN, the effect of the therapy on glomerular chemokine expression was significantly different between LN-CGN and V-CGN. It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68, MCP-1, and MIP-1α, but had no effect on MIP-1β in glomeruli with cellular crescents of patients with LN-CGN. In patients with V-CGN, the therapy also reduced the expression of CD68, but had no effect on MCP-1, MIP-1α, and MIP-1β in glomeruli with cellular crescents. It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in V-CGN as compared to LN-CGN. Conclusions The efficacy of steroid and CTX intermittent intravenous pulse therapy in CGN might be affected by reduction of glomerular chemokine expression. The different changes in glomerular expression of MCP-1 and MIP-1α in patients with LN-CGN and V-CGN after pulse therapy may correlate to different responses to treatment and prognosis.