α7nAChR激动剂对大鼠移植肺缺血再灌注损伤的保护作用

摘要

Objective To investigate the protective effect and possible mechanism of α7nAChR agonist (PNU 282987) on lung ischemia-reperfusion injury (IRI) by establishing rat allogeneic orthotopic left lung transplantation model. Methods The modified three-cuff anastomotic technique was used to establish the model of rat allogeneic orthotopic left lung transplantation. Healthy Sprague-Dawley male rats were randomly divided into 3 groups: sham operation group (group A), normal saline-treated IRI group (group B) and α7nAChR-treated group (group C). After the reperfusion for 4 h, the right pulmonary hilum was blocked for 5 min. The functions of the graft were checked by PaO2and PaCO2. Then the transplanted lung tissues were collected to measure the wet/dry ratio and the content of TNF-α and IL-6 by ELISA. Results Compared with the group A, PaO2decreased, while PaCO2, the wet/dry ratio and the content of TNF-α and IL-6 increased in the group B (P < 0.05). Compared with the group B, PaO2increased, simultaneously, the wet/dry ratio and the content of TNF-α and IL-6 decreased in the group C (P < 0.05); however, there was no statistical difference in PaCO2 between the two groups (P > 0.05). Conclusions α7nAChR agonist has protective effect on lung IRI after transplantation in rats and can improve lung functions by inhibiting inflammation.%目的 探讨α7nAChR激动剂对同种异体大鼠左肺移植后缺血再灌注损伤(I/R)的保护作用及其机制.方法 采用改良三袖套法技术复制同种异体大鼠左肺移植模型,将雄性SD大鼠随机分为3组:假手术组(A组)、生理盐水处理的I/R组(B组)和α7nAChR激动剂处理组(C组).受体移植肺再灌注4 h后阻断右肺门5 min,测量动脉血氧分压(PaO2)及动脉血二氧化碳分压(PaCO2);测量移植肺肺组织湿/ 干重量比率(W/D);采用ELISA法测移植肺中肿瘤坏死因子α(TNF-α)和白细胞介素6(IL-6)含量.结果 与A组比较,B组PaO2下降、PaCO2升高,肺组织W/D值升高,TNF-α及IL-6含量升高(P <0.05),差异有统计学意义.与B组比较,C组PaO2上升、肺组织W/D下降,TNF-α及IL-6含量降低(P <0.05),差异有统计学意义;PaCO2测定结果两组差异无统计学意义(P >0.05).结论 α7nAChR激动剂对大鼠肺移植缺血再灌注损伤具有保护作用,能够改善移植肺的功能,其作用机制可能与抗炎作用有关.