霉酚酸酯联合激素对弥漫增生性狼疮肾炎活动性及慢性病变的影响及其机制研究

Pathological effect of mycophenolate mofetil( MMF) and glucocorticoid on active and chronic lesions in diffuse proliferative lupus nephritis

目的 比较霉酚酸酯（ＭＭＦ）联合糖皮质激素治疗弥漫增生性狼疮肾炎前后肾组织的活动性和慢性病变的变化并探讨其机制。方法９例弥漫增生性狼疮肾炎患者在ＭＭＦ和糖皮质激素治疗后６～７个月接受了重复肾话检。应用天狼星红行胶原染色。Ｔ细胞、单核／巨噬细胞、增殖细胞、骨桥蛋白（ＯＰＮ）、纤连蛋白（ＦＮ）、α－平滑肌肌动蛋白（α－ＳＭＡ）及ＴＧＦ－β１应用ＳＰ法行免疫组织化学染色。计数细胞及应用图像分析对染色行定量评估。对组织病理表现行话动指数（ＡＩ）和慢性指数（ＣＩ）评分，观察上述指标在治疗前后的变化，分析其间的相关性。结果（１）治疗后ＡＩ下降，小球及小管间质浸润的Ｔ细胞、单核／巨噬细胞减少，小球及小管间质细胞的增殖率降低；ＯＰＮ表达减少并与小管间质的单核／巨噬细胞数正相关。（２）治疗后 ＣＩ变化不显著，ＦＮ在小球及小管间质的面积比、胶原在小管间质的面积比及。ＳＭＡ、ＴＧＦ－β１的表达在治疗前后差异无显著性意义。（３）治疗后间质的Ｔ细胞数与胶原在小管间质的面积比正相关，单核／巨噬细胞数与胶原、ＦＮ、α－ＳＭＡ在小管间质面积比正相关。结论ＭＭＦ联合糖皮质激素治疗弥漫增生性狼疮肾炎可以通过下调黏附分子减少单该巨噬细胞和淋巴细胞?

Objective To investigate the histopathologic alterations and the mechanisms of MMF combined glucocorticoid therapy in diffuse proliferative lupus nephritis(DPLN) Methods Nine patients with DPLN received re-biopsy after MMF and prednisone treatment for 6-7 months. T lymphocyte, monocyte/macrophage, proliferative cells, osteopontin(OPN), fibrinectin (EN), a-smooth muscle actin (αa-SMA), and TGF-β1 were detected by immunohistochemistry of SP method. Collagens were stained with Sirus red. Cells were counted and color image analytical system was applied to quantitate the staining. AI (active index) and CI (chronic index) were scored. The changes of above indicators were assessed and their correlations were analyzed. Results (1) After treatment, Al score decreased, T cells, monocytes/ macrophages infiltration, OPN expression and the percentage of proliferative cells in glomerulus and tubulointerstitium decreased significantly. (2) CL score didn‘t decrease significantly after treatment, the FN area ratio in glomerulus and tubulointerstitium, the collagen area ratio in tubulointerstitium and the expression of α-SMA and TGF-β1 were not reduced significantly. After treatment, inflammatory cell infiltration was correlated positively with the expression of EN. α-SMA and collagens in interstitium. Conclusions The active inflammatory lesions can be ameliorated through reduction of lymphocytes and monocytes/macrophages infiltration, inhibition of cell proliferation and down regulation of adhesion molecules. However, the chronic fibrotic lesions can not be reduced significantly.