胞外ADP激活血小板、形成微血栓是急性抗体介导排斥反应（Antibody-mediated rejection, AMR）中导致移植器官损伤的关键环节之一。目前研究表明，B细胞可表达三磷酸核苷双磷酸水解酶（NTPDase1）水解ADP，抑制血小板和血栓形成。但在急性AMR中，B细胞表达NTPDase1的水平及其对血小板活化和移植物损伤的效应和机制尚不清楚。本研究拟分别在NTPDase1转基因增强表达、基因敲除和野生型裸鼠皮肤移植模型上诱导急性AMR，比较不同裸鼠B细胞NTPDase1的表达量和活性、移植皮肤胞外ADP浓度及NTPDase1的mRNA和蛋白表达量、体内血小板位移实时动态影像和移植皮肤的病理变化，从分子水平和组织学水平分析急性AMR中，B细胞NTPDase1的表达量和活性与胞外ADP代谢的关系，探讨其对血小板活化、微血栓形成和移植皮肤损伤的效应及机制，开辟急性AMR治疗新途径。

Platelet activated by extracellular ADP and microthrombus emergence is one of important steps to damage the transplanted organ in acute antibody-mediated rejection (AMR). Recent studies indicated that B cell can express nucleoside triphosphate diphosphohydrolases 1 (NTPDase1). NTPDase1 can hydrolyze ADP and inhibit platelet activation and microthrombus emergence. But the NTPDase1 level expressed by B cell and its mechanism and effect to platelet activation and damage the transplanted organ in acute AMR is not clear. In our study, NTPDase1 transgenosis nude mice, NTPDase1 gene knock-out nude mice and wild type nude mice skin grafting model respectively will be induced acute AMR. The level and activity of NTPDase1 expressed by B cell, extracellular ADP concentration and the level of NTPDase1 mRNA in grafting skin, real time mobile image of platelet in blood vessel and pathological change of grafting skin in different nude mice will be compared. The relationship between the level and activity of NTPDase1 expressed by B cell and the metabolism of extracellular ADP in acute AMR will be analysed at molecules and histology level. The mechanism and effect of platelet activation, microthrombus emergence and its damage to the transplanted organ caused by extracellular ADP metabolized unbalance will be discussed. It will open new method to treat acute AMR in transplantation field.