α7nAChR 激动剂对大鼠移植肺缺血再灌注损伤的保护作用

Protective effect of α7nAChR against lung ischemia-reperfusion injury after transplantation in rats

摘要:

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。

Abstract:

Objective To investigate the protective effect and possible mechanism of α7nAChR agonist (PNU282987) 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 PaO2 and 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, PaO2 decreased, 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, PaO2 increased, 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.