霉酚酸酯治疗狼疮性肾炎伴血管病变患者血管内皮细胞损伤标记物的变化

The Change levels of endothelial biomarkers in mycophenolate mofetil treatment for patients with lupus nephritis presented with renal vasculopathy

目的 观察霉酚酸酯（MMF）治疗Ⅳ型狼疮性肾炎（LN）伴血管病变过程中,循环内皮细胞（CECs）、E-选择素（E-selectin）、血栓调节蛋白（TM）和血管内皮细胞黏附分子-1（VCAM-1）的变化,以期寻找无创的、反映MMF疗效的特异性分子标记物指导其治疗.方法 8例经肾活检诊断为Ⅳ型LN伴肾间质非炎症坏死性血管病变（NNV）或血栓性微血管病变（TMA）患者,甲基强的松龙（MP）静脉冲击治疗3天,诱导治疗均采用激素联合MMF,其中需肾脏替代治疗者4例.动态观察MMF治疗6个月患者CECs、E-selectin、TM和VCAM-1水平的变化.CECs采用免疫磁珠分离法计数,可溶性TM、VCAM-1和E-selectin水平均采用ELISA方法检测.结果 8例治疗均有效.MP及肾脏替代治疗前后CECs、TM、VCAM-1和E-selectin水平均无改变.MMF治疗6个月过程中,CECs与尿蛋白、尿红细胞、血肌酐水平呈正相关（p＜0.05）,与血浆白蛋白水平呈负相关（p＜0.05）.结论 CECs与MMF疗效呈显著相关性,CECs可能成为反映MMF疗效无创的分子标记物.

Objectives To explore the change levels of circulatory endothelial damage biomarkers, circulating endothelial cells （ CECs）, E - selectin, Thrombomodulin （ TM ） and vascular cell adhesion molecule-1（VCAM -1 ）, in MMF treatment for patients with lupus nephritis （LN） presented with renal vasculopathy. Methods A prospective study was performed on eight patients with class Ⅳ LN presenting with renal noninflammatory necrotizing vasculopathy （NNV） or thrombotic microangiopathy （TMA）. All patients were treated with mycophenolate mofetil （MMF） as induction therapy; four patients required initial renal replacement treatment on admission.The correlation between the change level of the biomarkers and the efficacy of MMF was investigated. CECs were isolated from peripheral blood with anti - CD - 146 - coated immunomagnetic Dynabeads, and the levels of TM, VCAM -1 and E-selectin were measured by ELISA. Results Therapeutic responses were achieved in all patients.There were no changes of the level of those biomarkers in patients required initial renal replacement treatment. A strong positive correlation was found between the level of CECs and proteinuria, urinary red blood cell count, serum creatinine（ p〈0.05）, and a negative correlation was observed between the level of CECs and serum albumin concentration（ p〈0.05）. Conclusions The decrease of CECs was associated with the amelioration of endothelial damage during MMF treatment for patients presented with lupus vasculopathy, thereby, CECs, provided dynamic detection, were considered as a promising marker to evaluate MMF therapeutic potential.