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山东大学学报(医学版) ›› 2013, Vol. 51 ›› Issue (11): 1-5.

• 基础医学 •    下一篇

单核细胞趋化蛋白-1和NF-κB通路在心脏移植排斥反应中的作用

白霄1，宋光民1，王维2，赵鑫1，赵宏磊1，赵文杰1，张健1   

  1. 1.山东大学齐鲁医院心外科, 济南 250012； 2.山东省胸科医院心血管中心, 济南 250013
  • 收稿日期:2013-06-17 出版日期:2013-11-10 发布日期:2013-11-10
  • 通讯作者: 宋光民， E-mail:songgm@sdu.edu.cn
  • 基金资助:

    山东省科技攻关计划 ( 2010GSF10246)；山东省自然科学基金 ( Y2007C056)

Effects of monocyte chemotactic protein-1 and NF-κB pathway in the rejection of cardiac allograft

BAI Xiao1, SONG Guang-min1, WANG Wei2, ZHAO Xin1, ZHAO Hong-lei1,ZHAO Wen-jie1, ZHANG Jian1   

  1. 1. Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan 250012, China;
    2. Cardiovascular Center, Thoracic Hospital of Shandong Province, Jinan 250013, China
  • Received:2013-06-17 Online:2013-11-10 Published:2013-11-10

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摘要：

目的  探讨单核细胞趋化蛋白-1(MCP-1)在心脏移植排斥反应中的表达及意义，并研究核因子-κB(NF-κB)通路在其中发挥的作用。方法  近交系SD大鼠为受体，Wistar大鼠为供体，“套管连接技术”行颈部心脏移植术。将SD大鼠随机平均分为4组，急性排斥组：受体未采用任何治疗；CsA组：移植术后环孢霉素A(CsA) 10mg/kg治疗受体，术后60～90d采集移植心脏；免疫耐受组：采用Wistar大鼠脾细胞(SPC)和环磷酰胺(CP)预处理SD大鼠，14d后行颈部心脏移植术；PDTC组：移植术后腹腔注射吡咯二硫氨基甲酸酯(PDTC)100mg/kg，1次/d，连续15d。Masson染色观察移植心脏纤维化程度，免疫组化及Western blotting检测MCP-1的表达。结果  急性排斥组、CsA组、免疫耐受组和PDTC组移植心脏存活时间分别为(6.53±2.48)d、(93.51±20.07)d、 (201.42±40.36)d和(142.37±24.64)d，PDTC组明显高于CsA组和急性排斥组(P＜0.05)，且心肌纤维化程度明显减轻。各组MCP-1表达的积分光密度(IOD)值依次为(1.86±0.23)、(1.58±0.16)、(0.57±0.15)及(1.16±0.28)，免疫耐受组明显低于其他３组，PDTC组显著低于急性排斥组和CsA组(P＜0.05)。结论  MCP-1的表达与排斥反应程度呈正相关，测定MCP-1的水平可预测移植心脏的功能状况；抑制NF-κB通路可减少MCP-1表达，明显减轻心脏移植排斥反应。

关键词: 移植排斥反应；核因子-κB；单核细胞趋化蛋白-1；吡咯二硫氨基甲酸酯

Abstract:

Objective  To investigate the expression and significance of monocyte chemotactic protein-1(MCP-1) in cardiac transplantation rejection as well as the role of nuclear factor of kappa B (NF-κB) pathway. Methods  Heterotopic cervical heart transplantation was performed on SD rats with Wistar rats as doners by using cuff-technique. The SD rats were randomly divided into 4 groups, with 12 in each group. Rats in the acute rejection group received no treatment. Rats in the CsA group were treated with 10mg/kg cyclosporine A after transplantation, and cardiac allografts were harvested 60 to 90 days after transplantation. Rats in the immunological tolerance group were pretreated with donor splenocyte (SPC) and cyclophosphamide (CP), and then heterotopic cervical heart transplantation was performed 14 days later. Rats in the PDTC group were treated with Pyrrolidine dithiocarbamate (PDTC) 100mg/kg every day for 15 days. The allograft myocardial fibrosis was then observed with Masson stain and the expression of MCP-1 was detected with immunohistochemistry and Western blotting. Results  The survival time of the cardiac allograft in acute rejection group, CsA group, immunological tolerance group and PDTC group was (6.53±2.48)d, (93.51±20.07)d, (201.42±40.36)d and (142.37±24.64)d respectively. The survival time of PDTC group was significantly longer than that of acute rejection group and CsA group (P<0.05), and the degree of myocardial fibrosis in PDTC group was much lower. The expression of MCP-1(IOD) of cardiac allograft in acute rejection group, CsA group, immunological tolerance group and PDTC group was (1.86±0.23), (1.58±0.16), (0.57±0.15) and (1.16±0.28) respectively. The IOD in immunological tolerance group was markedly lower than in the other three groups (P<0.05), and that in PDTC group was obviously lower than in acute rejection group and CsA group (P<0.05). Conclusion  The expression level of MCP-1 is positively correlated with the severity of graft rejection. As a result, the detection of MCP-1 can indicate the state of allograft. PDTC, as the inhibitor of NF-κB, can significantly relieve the rejection of cardiac allograft by inhibiting the expression of MCP-1.

Key words: Graft rejection; Nuclear factor of kappa B; Monocyte chemotactic protein-1; Pyrrolidine dithiocarbamate

中图分类号: 

  • R654.2
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