模拟肺移植后闭塞性细支气管炎小鼠模型的建立

A murine model of obliterative bronchiolitis after lung transplantation

目的为了更好地研究肺移植术后闭塞性细支气管炎(obliterative bronchiolitis,OB)的发病机制和预防治疗策略,建立一种稳定的小鼠闭塞性细支气管炎模型的方法。方法 20～25 g清洁级的C57BL/6,雄性,25只;BALB/c雄性,5只,按体质量配对分为两组,实验组A:BALB/c(n=5)→C57BL/6(n=10);对照组B:C57BL/6(n=5)→C57BL/6(n=10),进行气管原位移植。使用H-E染色,对比观察同种异体气管移植、同系气管移植和未进行气管移植小鼠闭塞性细支气管炎的发生情况。结果小鼠模型建立过程中病死率0%(0/20),术后4周病死率5%(1/20)。病理显示实验组小鼠气管内皮受损,黏膜下层有大量炎症细浸润,纤维组织增生,模型闭塞性细支气管炎的发生率为100%。而对照组均未发生OB,移植气管形态接近正常,无管腔狭窄。结论本研究成功地建立了模拟肺移植术后闭塞性细支气管炎的小鼠原位气管模型,为研究闭塞性细支气管炎的发病机制和预防治疗策略奠定了基础。

Objective To establish a murine model of obliterative bronchiolitis （OB） after lung transplantation. Methods Pathogen-free male C57BL /6 （ n = 25 ） and BALB / c （ n = 5 ） mice weighing 20 -25 g were used for experiments. Weight-matched mice were assigned to two groups for orthotopic tracheal transplant. Experimental group： the trachea from BALB / c （n = 5 ） was transplanted to C57BL /6 （n = 10 ）;Control group： the trachea from C57BL /6 （n = 5 ） was transplanted to C57BL/6 （n = 10） mice. Native and transplanted lungs were harvested, stained with H＆E, and examined under light microscopy. Results The mortality was 0% （0/20） during the process of model establishment and four-week mortality was 5% （1/20）. Pathology revealed the trachea endothelial cells in experimental group were damaged, accompanied by enhanced inflammatory cell infiltration and fibro hyperplasia. Incidence of obliterative bronchiolitis in mice of experimental group was approximately 100%, but control group showed no pathological changes in lung tissue. Conclusion Murine trachael transplantation model has been established successfully may be used to study the mechanism of OB.