PDTC对大鼠心脏移植排斥反应中MCP-1表达的干预

摘要

Objective To investigate the effect of pyrrolidine dithiocarbamate(PDTC) on monocyte chemotactic protein1 (MCP-1) in rejection of cardiac allograft and its mechanisms.Methods Heterotopic cervical heart transplantation was performed by cuff-technique.The SD rat recipients were randomly divided into 3 groups:AR group (Acute rejection,n =12),both the recipients and donors were without any treatment.CsA group(n =12),the recipients were treated with 10 mg/kg cyclosporine A after transplantation.PDTC group(n =12),the recipients were treated with 100 mg/kg PDTC after transplantation.All the cardiac allografts were harvested at different time post transplantation according to requirements.We studied allograft myocardial fibrosis wih the help of Masson stain,immuno-histo-chemistry and western blot also were used to detect the expression of MCP-1.Results The survival time of the cardiac allografts was significantly longer in PDTC group than in acute rejection group and CsA group(P ＜ 0.01),and myocardial fibrosis of cardiac allografts in PDTC group was significantly decreased (P ＜ 0.01).The IOD in PDTC group was markedly lower than in CsA group (P ＜ 0.01).Conclusion As the inhibitor of NF-κB,PDTC can significantly relieve rejection of cardiac allograft by inhibiting the expression of MCp-1.%目的 探讨吡咯二硫氨基甲酸酯(PDTC)对大鼠心脏移植排斥反应中单核细胞趋化蛋白-1(MCP-1)表达的影响及相关机制.方法 近交系SD大鼠为受体,Wistar大鼠为供体,各36只,雌雄不拘,体质量0.19 ～0.25 kg.按数字表法将供、受体大鼠随机分为3组,每组供、受体各12只.AR组(急性排斥组,供、受体均未采取治疗),CsA组[受体移植术后接受环孢霉素A(CsA) 10 mg/kg治疗],PDTC组(受体移植术后腹腔注射PDTC 100 mg/kg).采用“套管连接技术”行大鼠异位心脏移植术,术后不同时间按实验要求采集移植心脏.Masson染色观察移植心脏纤维化程度,免疫组化及Western blot技术检测MCP-1表达水平.结果 受体大鼠经PDTC治疗后,移植心脏存活时间较其它2组明显延长(P＜0.01),心肌纤维化程度显著减轻(P＜0.01),MCP-1在心肌组织中呈低水平表达(P＜0.01).结论 PDTC可明显抑制MCP-1在大鼠移植心脏中的表达,显著延缓移植排斥反应进展.