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大鼠气管异位移植慢性排斥反应模型的建立及其与白细胞介素17的关系
作者姓名:吴 东  李小军  刘茂林  王建军  翟 伟
作者单位:华中科技大学同济医学院附属协和医院胸外科,湖北省武汉市 430022;中山大学附属第三医院胸外科,广东省广州市 510630;十堰市东风公司总医院,湖北省十堰市 442000
基金项目:国家自然科学基金资助项目(30700767);教育部归国留学人员基金资助项目(2008890);湖北省自然科学基金(2013CFB088)
摘    要:背景:闭塞性细支气管炎是肺移植远期主要并发症之一,建立稳定可靠的动物模型是研究闭塞性细支气管炎的首要条件。 目的:建立大鼠气管异位移植慢性排斥反应模型,探讨白细胞介素17在该模型中的作用。 方法:按体质量配对,Wistar和SD大鼠随机分为2组(n=30):Wistar(供体)→SD(受体)组和SD(供体)→SD(受体)组,颈前皮下组织包埋移植气管,不同时间点分别采样行组织病理学分析,对比观察移植气管上皮丢失、淋巴细胞计数、无核软骨细胞/软骨细胞总数及白细胞介素17表达量等指标。 结果与结论:两组受体全部存活。移植后第7,14,28天两组淋巴细胞计数对比差异均有显著性意义(P < 0.05);移植后第14,28天两组无核软骨细胞/软骨细胞总数比值相比差异均有显著性意义(P < 0.05);移植后第7,14,28天Wistar(供体)→SD(受体)组上皮丢失度分别为> 40%,100%,100%,SD(供体)→SD(受体)组未见明显丢失;移植后第28天Wistar(供体)→SD(受体)组闭塞性细支气管炎发生率为100%,SD(供体)→SD(受体)组未发生闭塞。移植后第28天Wistar(供体)→SD(受体)组白细胞介素17表达量显著高于SD(供体)→SD(受体)组(P < 0.05)。以上结果说明实验成功建立了Wistar(供体)→SD(受体)大鼠异位气管移植慢性排斥反应模型,为闭塞性细支气管炎研究提供了平台,白细胞介素17可能在其中发挥重要作用。 中国组织工程研究杂志出版内容重点:肾移植;肝移植;移植;心脏移植;组织移植;皮肤移植;皮瓣移植;血管移植;器官移植;组织工程 

关 键 词:实验动物模型  移植动物模型  气管移植  大鼠  疾病模型  闭塞性细支气管炎  国家自然科学基金  
收稿时间:2015-09-07

Establishment of rat models of chronic rejection after heterotopic tracheal transplantation and the relationship with interleukin-17
Authors:Wu Dong  Li Xiao-jun  Liu Mao-lin  Wang Jian-jun  Zhai Wei
Institution:Department of Cardiothoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; Department of Cardiothoracic Surgery, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China; Dongfeng General Hospital of Shiyan City, Shiyan 442000, Hubei Province, China
Abstract:BACKGROUND: Obliterative bronchiolitis is one of the major complications of lung transplantation. Establishing a stable and reliable animal model is a prerequisite to the study of obliterative bronchiolitis. OBJECTIVE: To establish rat models of chronic rejection after heterotopic tracheal transplantation and investigate the effect of interleakin-17 in this model.  METHODS: After making donor/recipient pairs according to body weight, Wistar and Sprague-Dawley rats were  randomly divided into 2 groups (n=30): Wistar (donor)→SD (recipient) group and SD (donor)→SD (recipient) group. The trachea was embedded by recipient’s cervical subcutaneous tissue. Tracheal tissue was harvested at different time points for histopathological analysis. The indicators including epithelial loss, lymphocyte count, the ratio of anuclear chondrocyte number to total chondrocyte number and the expression level of interleukin-17 in the transplanted trachea were determined. RESULTS AND CONCLUSION: Recipients from these two groups all survived. At the 7th,14th and 28th days after transplantation, there was significant difference in lymphocyte count between these two groups (P < 0.05). At the 14th and 28th days after transplantation, there was significant difference in the ratio of anuclear chondrocyte number to total chondrocyte number between these two groups (P < 0.05). At the 7th, 14th and 28th days after transplantation, the degree of epithelial loss of rats in Wistar (donor)→SD (recipient) group was respectively > 40%, 100%, 100%, however, there was no obvious loss in the SD (donor)→SD (recipient) group. At the 28th day after transplantation, the incidence of obliterative bronchiolitis was 100% in Wistar (donor)→SD (recipient) group, however, no occlusion was observed in rats from the SD (donor)→SD (recipient) group. At the 28th day after transplantation, the expression level of interleukin-17 in Wistar (donor)→SD (recipient) group was significantly higher than that in the SD (donor)→SD (recipient) group (P < 0.05) These results demonstrate that Wistar (donor)→SD (recipient) rat models of chronic rejection after heterotopic tracheal transplantation were successfully established in this study, which provide a platform for the study of bronchiolitis obliterans. Interleukin-17 may play an important role in this field.  
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