摘要
目的建立肺移植后闭塞性细支气管炎动物模型,对其发病机制进行初步探讨。方法新鲜 SD 大鼠气管(每段5环)异位移植到 SD 大鼠(Ⅰ组)和 Wistar 大鼠(Ⅱ、Ⅲ组)腹腔并用大网膜包裹,Ⅰ、Ⅱ组不接受环孢菌素 A(CsA),Ⅲ组全程接受 CsA 10 mg·kg^(-1)·d^(-1)。分别在3、14、28 d后取出移植气管检测形态学改变和 Th1(IL-2、IFN-γ)/Th2(IL-4、IL-10)细胞因子表达,并观察 CsA 对上述指标的影响。结果术后3 d 时3组气管形态学变化差异无统计学意义(P>0.05)。14 d 时Ⅰ组气管形态基本恢复;Ⅱ、Ⅲ组上皮细胞几乎全部缺失,差异无统计学意义(P>0.05),与Ⅰ组区别明显(P<0.01);Ⅱ组管腔阻塞(28.5±5.0)%,淋巴细胞密集浸润,Ⅲ组阻塞(19.4±2.9)%,较多淋巴细胞分布,3组差异有统计学意义(P<0.01)。28 d时Ⅰ组形态正常,Ⅱ组管腔阻塞(94.8±3.6)%,浸润淋巴细胞有所减少,Ⅲ组阻塞(36.6±7.6)%,淋巴细胞分布减少,3组差异有统计学意义(P<0.01)。Ⅱ组 Th1/Th2细胞因子表达比Ⅰ组明显升高。与Ⅰ组相比,Ⅱ组 Th1细胞因子表达比 Th2细胞因子升高更为显著。Ⅲ组 IL-2表达比Ⅱ组明显减少,但2组 IFN-γ、IL-4、IL-10表达差异没有统计学意义。结论同种异体移植物在上皮细胞损害、纤维性细胞增生以及淋巴细胞浸润等方面较同系移植物有明显变化。Th1/Th2促进了同种异体大鼠异位移植气管闭塞性细支气管炎(OB)的发生,其细胞因子可能介入了 OB 的发病机制。CsA 减少管腔阻塞和淋巴细胞浸润,但对于移植物上皮没有明显保护作用。CsA 抑制 IL-2基因转录,在一定程度上减少了 OB 病理性损害。
Objective To establish an animal model of obliterative bronchiolitis （OB） after lung transplantation and investigate the pathogenesis preliminarily. Methods Tracheal segments （5 cartilaginous rings each） were transplanted from SD rats to SD rats （Group Ⅰ） or to Wistar rats （Group Ⅱ and Ⅲ ）. Grafts were implanted into an abdominal cavity and wrapped in the omentum. Animals in Group Ⅰ and Ⅱ did not receive CsA, animals in Group Ⅲ received CsA daily by gastrotube at 10 mg· kg^-1· d^-1 from beginning to end. Grafts were harvested on day 3,14 , 28 after transplantation as representative time points for 3 phases of injury in the evolution of allograft airway obliteration, then examined histological changes and gene expression of T-helper 1-and T-helper 2-type cytokines [ Th1 ： interleukin-2 （ IL-2 ）, interferon-gamma （IFN-γ） ; Th2：interleukin-4 （IL-4） , interleukin-10 （IL-10） ]in grafts. At the same time, effects of CsA were observed on the above-mentioned indices. Results There was no significant difference in histological changes on day 3 after transplantation among 3 groups （ P 〉 0. 05 ）. Tracheas in Group Ⅰ approached to normal morphology on day 14 after transplantation. Airway epithelium of Group Ⅱ and Ⅲ almost lost completely on day 14 after transplantation. There was no significant difference between Group Ⅱ and Group Ⅲ（ P 〉 0. 05 ）, but there were significant differences between Group Ⅰ and Group Ⅱ or Group In. The cross-sectional area of the tracheal lumen was narrowed by approximately （5.0 ± 1.2 ） %, （ 28.5 ± 5.0） % and （19. 4 ± 2. 9 ）% respectively on day 14 after transplantation in Group Ⅰ, Ⅱ and Ⅲ, there were significant differences among 3 groups. On day 14 after transplantation, tracheas in Group Ⅰ revealed few lymphocytic infiltration, but it showed dense lymphocytic infiltration in Group Ⅱ. Tracheas in Group Ⅲ have much more lymphocyle infiltration than that in Grouup Ⅰ, but much less than in Guoup Ⅱ, There were significant differences among 3 groups, too （P〈0.01）. The tracheal lumen revealed almost total luminal obstruction （94.8±3.6）% on day 28 after transplantation in Group Ⅱ, The cross-scctional area of the tracheal lumen was narrowed by approximately （3.7±0.8）% and （36.6±7.6）% respectively in Group Ⅰ and Ⅲ on day 28. There were significant differences among 3 groups （P〈0.01）. Compared with that on day 14, lymphocytic infiltration had decreased gradually on day 28 in Group Ⅱand Ⅲ. There were significant differences among 3 groups all the same （P〈0.01）. In Group Ⅰ, expression of IL-2, IFN-γ, IL-4 ,and IL-10 were much higher than that in Group Ⅰ.Expression of Th1 cytokines was inereased to a greater extent than that of Th2 cytokines in Group Ⅱ compared with Group Ⅰ. Allografts in Group Ⅲ expressed signifieantly less IL-2 gene transcripts than that in Group Ⅱ over all the points. There was no significant difference between Group Ⅰ and Ⅲ in IFN-γ, IL-4 and IL-10 gene expression . Conclusions Compared with isografts. allografts have more obvious changes, such as epithelial damage, fibroprolifetation and lymphocytic infiltration. Th1 and Th2 lymphocyte subtypes contribule to the development of obliterative bronchiolitis in heterotopic trachea transplant model of rat, and changes of their cytokines gene epression may be involved in the pathogenesi. CsA could reduce the development of fibroprolife-ration and lymphocyte infiltration markedly, but it could not protect airway epithelium. CsA inhibits IL-2 gene transcripts, so it can reduce development of the pathologic lesion of obliterative bronchiolitis to a certain degree.
出处
《中华外科杂志》
CAS
CSCD
北大核心
2007年第4期262-266,共5页
Chinese Journal of Surgery
关键词
肺移植
细支气管炎
闭塞性
鼠科
肺疾病
阻塞性
Lung transplantation
Bronchiolitis
obliterans
Muridae
Lung diseases, obstructive
