中文摘要：

目的探讨树突状细胞（DC）在肾小管间质炎症损伤中的作用，以及抗P-选择素功能域单抗（PsL—EGFmAb）对Dc浸润及体外成熟与功能的干预调节。方法（1）建立大鼠单侧输尿管梗阻（UUO）模型。分别采用免疫组化和免疫双染与图像分析，观察P-选择素及CDla’CD80＋DC在肾组织表达和分布变化。（2）从脐血CD34＋造血干细胞中诱导扩增DC，并于成熟过程中采用流式细胞仪分析细胞表面分子表达；RT-PCR检测细胞NF—KBP50、P65mRNA表达；混合淋巴细胞反应（MLR）检测DC对T细胞刺激能力；以及ELISA测定MLR上清液IL-12p70分泌含量。结果（1）与假手术组比较，UUO大鼠从第1天起，随着P-选择素以肾小管上皮细胞为主的小管间质表达。CDla＋CD80＋DC以肾间质为主浸润；至第7天P-选择素上调且CDla’CD80＋DC显著聚集。两者明显相关且与肾小管间质病变程度显著相关。经PsL．EGFmAb处理后，大鼠肾组织P-选择素表达下调，CDla＋CD80＋DC浸润减少，且肾小管间质损害程度减轻。（2）经TNF-α刺激炎性状态下，培养人DC成熟过程中基本不表达或低表达P-选择素，但持续高表达与P-选择素同属C型凝集素的DC-SIGN。经PsL—EGFmAb处理后，可明显抑制DC-SIGN及细胞内NF—κB基因表达，并相应抑制DC黏附共刺激分子表达、IL．12分泌及刺激T细胞增殖能力。结论DC也是肾小管间质炎症病变启动因素。针对P-选择素功能域的单抗对其浸润具抑制作用。此外，该单抗对人DC成熟与功能有调节效应，提示与抑制作为DC模式识别及黏附受体的DC-SIGN有关．并可能通过影响NF—κB途径起作用。

英文摘要：

Objective To explore the distribution of dendritic cells（DCs） and the expression of adhesion molecules in rat kidney with unilateral ureteral obstruction （UUO）,as well as the regulatory effect of anti-P-selectin lectin-EGF domain monoclonal antibody （PsL-EGFmAb） on adhesion, maturation and function of human DCs cultured in vitro. Methods UUO rat models were established, which were divided into sham group （n=6）,untreated group （n=18）and treated group with PsL-EGFmAb （n=18）, DCs were analyzed with Axioplan 2 microscopy, while P-selectin being observed by immunohistochemistry. CD34^＋ stem cells were isolated from cord blood and cultured in 20%IMDM medium with SCF, GM-CSF, TGF-β1, FIt-3L and TNF-α in vitro. During development, PsL-EGFmAb was added and IL-10 served as control. FACS was performed to detect the expression of HLA-DR, CDla, CDllc, CD54,CD83, CD80, CD86, CD209 （DC-SIGN） and CD62-P,-E,-L （P-,E-,L-selectin） on DCs. RT-PCR was performed to detect the expression of NF-KB P50, P65 mRNA. MLR was performed to detect the stimulatory effect of DCs on T cell proliferation and ELISA to determine IL-12p70 amount. Results Comparing with Sham group, the expression of P- selectin was up-regulated among tubulointerstitium mainly on renal tubular epithelial cell after unilateral ureteral obstruction on day 1, while CDla＊CD80＋DCs being also found in renal interstitium. The expression of P-selectin and CDla＋CD80＊DCs was increased evidently on day 7, and correlated with the degree of renal tubulointerstitial fibrosis closely. However, these changes became less conspicuous in rat treated with PsL-EGFmAb. In vitro experiment showed on day 5 after cultured with the induction of TNF-α, immature DCs highly expressed C-type lectin DC-SIGN of pattern recognition receptors; the expression of co-stimulatory molecules such as CDllc,CD83,CD80 and CD86 on mature DCs was up-regulated in paralleling with the mRNA level of NF-KB;the secretion of IL-12 was enhanced, as well as displaying the featu