鼠纤维介素在小鼠心脏移植急性排斥反应中的表达及其意义

目的　探讨小鼠同种心脏移植急性排斥反应期间鼠纤维介素 (mfgl2 )在移植心脏组织中的表达及其与组织病理学改变的关系。方法　采用BALB/c小鼠到C5 7BL/ 6小鼠的颈部异位心脏移植作为同种排斥反应模型 ,以抗mgfl2多克隆抗体干预 ,并设同系小鼠心脏移植对照组。采集移植心组织标本作病理学检查 ,以免疫组织化学方法测定mfgl2在移植心脏组织细胞上的表达 ,并对mgfl2的表达进行半定量分析。结果　同系移植对照组移植心脏组织结构正常 ,未见mfgl2表达 ;同种移植组移植心脏组织出现进行性坏死 ,大量单个核细胞浸润 ,并伴有mfgl2的表达 ,且血管内皮细胞表达mfgl2 ;抗mfgl2抗体干预组移植心脏组织损伤较轻 ,移植物的存活时间延长 (P <0 .0 1) ,巨噬细胞、淋巴细胞的浸润和mfgl2表达量也显著减少。结论　mfgl2表达水平与排斥反应所致移植心脏病理损害程度相关 ;抗mfgl2抗体干预能显著减少移植心脏巨噬细胞、淋巴细胞的浸润 ,明显延长移植心脏存活时间。

Expression of mfgl2/fibroleukin in mouse cardiac allograft and its potential clinical implication

Objective To investigate the expression of mfgl2/fibroleukin in mouse cardiac allograft and its potential clinical implication. Methods The mouse model of cervical heterotopic cardiac transplantation was used. The mice were divided into three groups: a) cardiac isograft of C57BL/6 to C57BL/6 mice; b) cardiac allograft of Balb/c to C57BL/6 mice; c) cardiac allograft of Balb/c to C57BL/6 mice with mfgl2 polyclonal antibody treatment. The grafts were collected at indicated time points and snapped frozen for further use. Histological sections were stained with hemotoxylin and eosin. A polyclonal antibody against mfgl2 was used to detect the expression of mfgl2 protein by immune histochemistry. Anti-CD68 monoclonal antibody was also used to detect the macrophages activation. Semi-quantitative measurement of mfgl2 expression in the grafts was done with Multimedia Pathology Imaging Analysis System (MPIAS). Results The mfgl2 expression was detected in endothelial cells, macrophages (CD68 positive) located selectively in the areas of acute focal, confluent necrosis in mice receiving cardiac allograft transplantation (Balb/c to C57BL/6 mice); There was much more mfgl2 expression within the grafts with severe myocardium necrosis on the day 7 than that on the day 3 examined by histological observation as well as semi-quantitative measurement by MPIAS. There was much less macrophage and mononuclear cell's infiltration and the grafts survival was 9.4 days on average with the mfgl2 polyclonal antibody treatment compared with 7.3 days in the control. No mfgl2 protein expression was detectable in mice receiving cardiac isograft transplantation (C57BL/6 to C57BL/6 mice), which showed normal histological structure. Conclusion The expression level of mfgl2 was correlated with the progression of myocardium necrosis within the grafts in allograft transplantation. mfgl2 polyclonal antibody treatment could significantly improve the histological damage and prolong the graft suvival.