联合药物预处理对非协调性异种心脏移植物的影响

目的　观察联合应用环孢素A(CsA)和来氟米特 (Lef)预处理对豚鼠 大鼠非协调性异种心脏移植物的影响并探讨其作用机制。方法　移植大鼠分为 4组 :A组 (CVF ,n =10 ) ;B组(CVF CsA ,n =8) ;C组 (CVF Lef,n =5 ) ;D组 (CVF CsA Lef ,n =11) ;记录移植物存活时间 ,检测移植物病理组织学 ,用免疫组织化学检测移植物CD68、CD5 7表达情况 ,TUNEL法检测移植物细胞凋亡。结果　移植物的平均存活时间 :A组为 41h、B组为 68h、C组为 5 5h、D组为 82h。各组移植物病理表现均为急性血管性排斥反应 (AVR)改变。B、C、D组移植物炎症细胞浸润数减少 ,CD68和CD5 7表达下调 ,凋亡指数较低 ,半定量测定与A组比较差异有显著性 (P <0 .0 5 ) ;D组凋亡指数最低而CD68和CD5 7表达最弱 ,与其他各组比较差异有显著性 (P <0 .0 5 )。结论　联合应用CsA和Lef预处理可明显延长非协调性异种移植物存活时间 ,减少炎症细胞浸润 ,抑制心肌细胞凋亡 ,减轻异种AVR损害。

Effect of combined drugs pretreatment on discordant cardiac xenografts

Objective To investigate the effect of pretreatment of cyclosporin A (CsA) in combination with leflunomide (Lef) on guinea pig-to-rat discordant cardiac xenografts.Methods The rats were divided into 4 groups: group A (CVF,n=10);group B (CVF CsA,n=8);group C (CVF Lef,n=5);group D (CVF CsA Lef,n=11).The survival time of xenograft was measured and the histopathologic observation was carried out after the graft arrest and results were compared and analyzed.The expression of CD68 and CD57 in xenografts was detected by using immunohistochemical staining method.Apoptosis in xenografts was determined by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and apoptotic index (AI) were analyzed.Results The mean survival time of cardiac xenograft was 41 h in group A,68 h in group B,55 h in group C,and 82 h in group D respectively.Histological changes of AVR were shown in all groups and the number of inflammatory cell infiltration in xenografts of group B,group C and group D was less than that of group A.There was weak expression of CD68 and CD57 in xenografts and lower AI in group B,group C and group D than those in group A by semi-quantitative determination (P< 0.05).The AI was significantly lowest and the CD68 and CD57 expression was weast in group D (P< 0.05).Conclusion Combination of CsA and Lef pretreatment can significantly prolong discordant xenograft survival time,ameliorates infiltration of macrophages and nature killer cells,attenuate myocardial cell apoptosis and thus alleviate pathological lesion of acute xenograft vascular rejection.