静脉注射用免疫球蛋白抑制异种移植超急排斥反应的作用机制  

Studies on mechanisms of inhibiting hyperacute rejection in pig-human xenotransplantation by intravenous immunoglobulins

作　　者：卢锦山[1] 肖序仁[1] 敖建华[1] 高江平[1] 洪宝发[1] 

机构地区：[1]解放军总医院泌尿外科,北京100853

出　　处：《中国现代医学杂志》2005年第8期1177-1181,共5页China Journal of Modern Medicine

摘　　要：目的探讨猪-人非协调性异种移植中超急性排斥反应(HAR)及静脉注射用免疫球蛋白(IVIG)抑制HAR的作用机制。方法以体外游离器官血液灌注系统为基础,建立猪-人异种器官移植模型。实验分A、B、C即人血灌注、人血加IVIG灌注和猪血灌注三组,观察HAR的发生并进行血清补体及其活性的检测以及组织病理和免疫荧光的研究。结果A组移植器官发生HAR的平均时间为(39.3±11.2)min,B、C两组的移植器官在180min内未发生HAR。A组移植器官的组织病理学研究可见广泛微血栓形成和中性粒细胞浸润,B、C两组则无明显的病理改变;免疫荧光研究还发现A、B两组的移植器官沿其肾小球毛细血管有明显的IgM和补体C1q的沉积,A组移植器官则另有显著C3沉积而B组未见;B组加用IVIG前后,其血清补体C3和总补体溶血活性水平均无明显变化;A、B两组移植器官灌注过程中均有大量的血清补体C4消耗。结论IVIG抑制猪-人非协调性异种移植HAR的机制在于,阻止补体激活经典途径中C3和其后的补体活性成分在异种移植物内皮细胞表面的沉积或附着,籍此保护移植物内皮细胞免于活化和损伤。[Objective]To study the hyperacute rejection (HAR) in pig - human discordant xenotransplantation and the mechanism of inhibiting HAR by intravenous immunoglobulin (IVIG). A pig-human xenogeneic organ transplantation model was erected based on an in vitro free organ blood perfusion system. The experiment was divided into Group A (human blood perfusion), Group B (human blood plus IVIG perfusion) and Group C (porcine blood perfusion), in order to observe HAR occurrence, detect serum complements, as well as make histopathological and immunofluorescence studies. The mean time of HAR occurrence by transplanted organs in Group A was (39.3±11.2) min while no HAR occurrence by transplanted organs in Groups B and C within 180min. Histopathological studies showed that extensive formation of microthrombi and infiltration of neutrophilic granulo1cytes were identified in the transplanted organs in Group A whilst no obvious pathological changes were found for the transplanted organs in Groups B and C. Immunofluorescence studies also indicated there had distinct IgM and C1q sedimentation along the glomerular capillary of the transplanted organs in Groups B and C; Besides, notable C3 deposit was found in the transplanted organs in Group A and no such deposit was found in Group B. Before and after using IVIG for Group B, no change in the level of hemolytic activities for its C3 and total complements. In the course of perfusion, there were large quantities of consumption of serum C4 by the transplanted organs in Groups A and B. [Conclusion] The mechanism of inhibiting HAR in pig-human discordant xenotransplantation by IVIG lies in the prevention of first, complements from activating C3 in classical pathways, and then, the elements of the complements activity from sedimentation on, or attachment to, the surface of transplanted endothelial cells. By doing so, the endothelial cells of the transplanted organ are protected from activation and injuries.

关 键 词：异种移植 排斥反应 免疫球蛋白 

分 类 号：Q512.2[生物学—生物化学]