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山东大学学报(医学版) ›› 2012, Vol. 50 ›› Issue (6): 38-.

• 基础医学 • 上一篇    下一篇

趋化因子RANTES和受体CCR5在心脏移植慢性排斥反应中的表达

张远浩,宋光民,赵文杰,白宵,张敬国,赵鑫   

  1. 山东大学齐鲁医院心外科, 济南 250012
  • 收稿日期:2011-12-12 出版日期:2012-06-10 发布日期:2012-06-10
  • 通讯作者: 宋光民(1963- ),男,教授,博士生导师,主要从事心脏移植的研究。 E-mail: songgm@sdu.edu.cn
  • 作者简介:张远浩(1986- ),男,硕士研究生,主要从事心脏移植的研究。
  • 基金资助:

    山东省科技攻关计划资助项目(2010GSF10246);山东省自然科学基金资助项目(Y2007C056)。

Expression and significance of RANTES and CCR5 in
chronic rejection of cardiac allografts

ZHANG Yuan-hao, SONG Guang-min, ZHAO Wen-jie, BAI Xiao,
ZHANG Jing-guo, ZHAO Xin   

  1. Department of Cardiovascular Surgery, Qilu Hospital of Shandong University, Jinan 250012, China
  • Received:2011-12-12 Online:2012-06-10 Published:2012-06-10

摘要:

目的   探讨调节活化正常T细胞表达和分泌因子(RANTES)及其受体CCR5在心脏移植慢性排斥反应中的表达及意义。方法   健康近交系SpragueDawley(SD)大鼠为受者,Wistar大鼠为供者,采用“套管连接技术”建立颈部心脏移植的实验模型。将SD大鼠随机分为3组:A组(n=12)供、受者均未采用任何治疗;B组(n=12)移植手术后使用环孢素A(CsA)10mg·kg-1治疗受者,术后2~3个月采集移植心脏;C组(n=24)使用供者脾细胞(SPC)及环磷酰胺(CP)预处理受者,其中12只在术后15~60d采集移植心脏(C1组),另外12只术后至少观察半年(C2组)。采用HE染色观察移植心脏组织排斥反应病理改变程度,Van Gieson染色观察移植心脏血管病变(CAV)的血管狭窄程度,免疫组化检测RANTES和CCR5的表达水平。结果   SPC和CP预处理后,移植心脏的存活时间明显延长,RANTES和CCR5在冠状血管和心肌组织中呈低水平表达,移植心脏血管病和心肌纤维化明显减轻;而在急性排斥反应和CsA治疗的移植心脏组织中,RANTES和CCR5的表达水平明显增强,差异有统计学意义(P<0.05)。结论   移植心脏组织中RANTES和CCR5的表达水平与移植排斥反应的程度密切相关。

关键词: 移植心脏血管病;心肌纤维化;趋化因子及趋化因子受体;大鼠

Abstract:

Objective   To investigate expressions of regulation upon activation of normal T-cell expressed and secreted(RANTES) and CCR5 in the chronic rejection of cardiac allografts. Methods   Cervical cardiac transplantation by cuff-technique was performed from Wistar rats to Sprague-Dawley (SD) rats. The SD rat recipients were randomly divided into 3 groups: (A) (n=12) Both the recipients and the donors were without any treatment. (B)(n=12) The recipients were treated with 10mg/kg-1 cyclosporine A after transplantation and euthanized 2 to 3 months later. (C)(n=24) The Sprague-Dawley rat recipients were pretreated with donor splenocyte (SPC) and cyclophosphamide (CP). Half were euthanized 15-60 days after transplantation(C1) and the other half were monitored for at least 6 months after transplantation(C2). Pathological change of the allograft caused by the rejection was observed by H-E staining. Cardiac allograft vasculopathy (CAV)was observed by Van Gieson staining. Expressions of RANTES and CCR5 were monitored by immunohistochemistry.  Results   Pretreatment of animals with SPC and CP induced long-term cardiac allograft survival. Immunohistochemical staining demonstrated a low level of RANTES and CCR5 expressions in the cardiac allograft muscles and coronary arteries in Group C. In contrast, expressions of RANTES and CCR5 in the cardiac allografts of Groups A and B were significantly higher than those in Group C (P<0.05). The CAV and myocardial fibrosis were dramatically reduced in Group C compared with those of Groups A and B (P<0.05).  Conclusion   Expressions of RANTES and CCR5 in cardiac allografts may play an important role during the development of chronic rejection.

Key words:  Cardiac allograft vasculopathy; Myocardial fibrosis; Chemokine and chemokine receptor; Rats

中图分类号: 

  • R654
[1] 孟祥斌1,毕研文1,冯进波2,张建平3,岳韦名4,宋光民1,孙文宇1. 核因子κB的小干扰RNA防治自体移植静脉再狭窄的实验研究[J]. 山东大学学报(医学版), 2010, 48(11): 74-80.
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