摘要
目的 :进一步阐明霉酚酸酯 (MMF)对难治性Ⅳ型狼疮性肾炎 (LN)患者肾组织学改变的影响 ,探讨MMF作用机制。 方法 :对 15例接受MMF治疗 (0 .75～ 1.5 g/d)的难治性Ⅳ LN患者进行重复肾活检 ,穿刺组织分别作常规光镜、免疫荧光检查。肾小球系膜区基质增生及肾小管间质半定量分析借助MAPIS 5 0 0多媒体病理彩色分析系统。肾组织CD4+ 与CD8+ 细胞染色、细胞间粘附分子 1(ICAM 1)和血管细胞粘附分子 1(VCAM 1)表达采用PAP四层法。观察治疗前后上述各项指标的改变。 结果 :①MMF治疗后肾组织活动性指数明显减少(P <0 .0 1) ,平均肾小球细胞计数 (P <0 .0 1)、肾小球毛细血管袢坏死发生率 (P <0 .0 5 )、肾小球毛细血管内血栓形成发生率 (P <0 .0 1)和细胞性新月体发生率 (P <0 .0 1)均较治疗前明显减少。但肾小球系膜区基质增生较治疗前增加 (P <0 .0 5 ) ,肾小球硬化、慢性化指数与治疗前相比较无统计学差异。②MMF治疗后肾小球内浸润的CD6 8+ 、增殖细胞核抗原阳性 (PCNA+ )细胞较治疗前明显减少 (分别为P <0 .0 1,P <0 .0 5 )。肾间质CD4+ 细胞、CD8+ 细胞、CD6 8+ 细胞和PCNA+ 细胞治疗前后均无明显变化。③MMF治疗后肾小球ICAM 1和VCAM 1表达均较治疗前明显减少 (均为P <0 .0 1) ,肾间质除平均ICAM
To evaluate the effect of mycophenolate morfetil (MMF) on renal histopathology of refractory severe lupus nephritis and its mechanism. METHODOLOGY Fifteen patients of refractory lupus nephritis were included in this study.All the patients received renal biopsy before and after MMF treatment (0 75 1 5g/day)for 3 months.All samples were routinely processed for optical and immunofluorescence microscopy.In the assessment of glomerular mesangial expansion and tublo interstial lesion,MAPIS 500 multi media color image analytical system was applied.Renal CD4 + and CD8 + cell,proliferative cell nuclear antigen(PCNA) + cell,intercellular adhesion molecule 1,vascular cell adhesion molecule 1 were analyzed by immunohistochemistry of 4 layer PAP method. RESULTS ①The activity index reduced significantly from 16 4±7 82 to 4 05±2 04( P <0 01),number of cell per glomerulus from 173±42 8 to 135±19 0( P <0 01),patients with glomerular capillary necrosis from 11/15 to 0/15( P <0 05),patients with glomerular capillary thrombosis from 7/15 to 0/15( P <0 05),the patients with cellular crescents from 11/15 to 0/15( P <0 05),while ratio of mesangial/glomerular area significantly increased from 29 3±4 62 to 35 8±8 78( P <0 05)after treatment.No statistical difference was found in chronic index(1 72±1 03 vs 2 81±2 82)and ratio of interstitial area/interstial and tubular area(28 3±7 78 vs 26 6±8 34)(both P >0 05).?②The CD68 + cell per glomerulus(12 6±7 22 vs 1 64±2 32, P <0 01),the PCNA + cell per glomerulus (0 965±0 883 vs 0 357±0 275, P <0 05)decreased significantly after treatment.On the other hand,the CD4 + cell/mm 2,CD8 + cell/mm 2,CD68 + cell/mm 2,PCNA + cell/mm 2 of interstitium was not found to change significantly.?③The glomerular expression of ICAM 1( P <0 01)and VCAM 1( P <0 01)decreased significantly after treatment.The mean percentage of ICAM 1 + tubule decreased significantly (19 3±14 8 vs 9 14±9 66, P <0 01),while ICAM + cell/mm 2,VCAM 1 + cell/mm 2 of interstitium and the mean percentage of ICAM 1 + tubule had no obvious variant after treatment. CONCLUSION MMF(0 75 1 5g/day)is effective for active glomerular lesion of refractory severe lupus nephritis,by a mechanism in which inhibition of glomerular adhesion molecule expression might be involved.
出处
《肾脏病与透析肾移植杂志》
CAS
CSCD
2000年第1期18-22,共5页
Chinese Journal of Nephrology,Dialysis & Transplantation
