急性抗体介导排斥反应中微血栓形成对移植物损伤的机制研究  

The mechanism of microthrombosis and its damage to graft in acute antibody-mediated rejection

作　　者：张勇[1] 王雅梅[1] 宗焕涛[1] 杨称称[1] 崔元善[1] 

机构地区：[1]首都医科大学附属北京天坛医院,北京100050

出　　处：《中国免疫学杂志》2013年第4期377-381,共5页Chinese Journal of Immunology

基　　金：国家自然科学基金资助项目(81270838);北京市自然科学基金资助目(7123213)资助

摘　　要：目的:探讨急性抗体介导排斥反应(Antibody-mediated rejection,AMR)中微血栓形成对移植器官损伤的效应及机制。方法:在三磷酸核苷双磷酸水解酶(NTPDase1)野生型裸鼠皮肤移植模型上诱导急性AMR,用实时荧光定量PCR、倒置显微镜等方法,研究B细胞NTPDase1的表达活性、移植皮肤NTPDase1 mRNA表达量、血小板活化标记物和血小板移动平均速率测定值,及移植皮肤病理变化;补充外源性NTPDase1预处置对血小板活化和移植皮肤损伤的影响。结果:急性AMR发生时,B细胞NTPDase1的表达上调,移植皮肤的NTPDase1 mRNA表达下降,血小板活化、移植皮肤受损;NTPDase1预处置可有效抑制血小板活化、保护移植皮肤。结论:NTPDase1降解胞外ADP失衡可能是急性AMR中移植物损伤的主要原因,中剂量外源性NTPDase1预处置保护移植物有效、安全。Objective ：To study the mechanism of microthrombosis and its damage to graft in acute antibody-mediated rejection （AMR）. Method： The acute AMR animal model in male nucleoside triphosphate diphosphohydrolases 1 （NTPDasel） wild-type BALB/c athymic nude mice was established. The level of NTPDasel expressed by B cell, the level of NTPDasel mRNA in grafting skin, platelet activation markers, real time mobile image of platelet in blood vessel and pathological change of grafting skin in different nude mice were compared by real-time fluorescent quantitative PCR and inverted microscope. Effects of pretreatment with different doses of exogenous NTPDase 1 on platelet activation and graft injury were determined. Results：The expression of B-cell NTPDasel was signicantly increased after the induction of acute AMR. The levels of NTPDasel mRNA in grafted skin were decreased. And the platelet were activated, the grafted skin were damaged after the induction of acute AMR. NTPDasel pretreatment can inhibit platelet activation and protect grafted skin. Conclusion：An imbalance in the NTPDasel-induced degradation of extra cellular ADP may be a major cause of graft injury in acute AMR. Pretreatment with exogenous NTPDasel may effectively inhibit platelet activation and protect grafted skin.

关 键 词：三磷酸核苷双磷酸水解酶 B细胞 ADP 急性抗体介导排斥反应 移植 

分 类 号：R392.11[医药卫生—免疫学]