白介素1β及其受体拮抗蛋白在肠缺血/再灌注诱导肺损伤中的作用和机理

The role and mechanism of interleukin 1β and its receptor antagonist in lung injury induced by gut ischemia/reperfusion

目的:探讨肠缺血-再灌注(I/R)损伤时肺损伤的机理及白介素1β(IL-β)及其受体拮抗蛋白的作用。方法:采用大鼠肠系膜上动脉夹闭造成I/R损伤模型。利用放射免疫分析测定损伤前后和各处理组血液、肺组织灌注液中IL-1β和IL-1ra水平。同时采用RT-PCR法测定肺组织中IL-1β和IL-1ra的mRNA的表达含量。经光镜和电镜观察肺局部白细胞浸润及组织损伤情况。结果:I/R损伤后6小时血液中IL-1β和IL-1ra有所增加,即表现为损伤组IL-1β比对照组明显增加,而IL-1ra不明显;但IL-1ra的损伤组和对照组二者均在损伤后6小时比伤前自身对照组明显增加。肺组织灌洗液中损伤组IL-1β明显增多,而IL-1ra不明显。肺组织中IL-1β的mRNA在损伤后表达明显增加,而IL-1ra表达没有明显变化。经非特异性磷脂酶A_2(PLA_2)阻断剂(氯喹和三氟拉嗪),血小板活化因子受体阻断剂SR27417A,环氧化酶抑制剂消炎痛以及抗氧化剂愈创木酸等处理后,血清、肺灌注液和肺组织中上述指标有不同程度的改变。肺内白细胞的聚集和浸润明显减少。结论:IL-1β和IL-1ra可能参与肠I/R介导急性肺损伤,并且同局部PLA_2活化有一定关系。

Objective: To investigate the role of interleukin 1β and its receptor in lung injury after gut ischemia/ reperfusion (I/R). Methods: Rat I/R injury was produced by clamping the superior mesenteric artery for 60 min. The levels of IL-1β and IL-1ra in blood and lung tissue perfusion liquid were analyzed by radioimmunoassay before and after injury in each experimental group. The mRNA expressions of IL-1β and IL-1ra in lung tissue were assessed with RT-PCR. Leukocytic infiltration and local tissue damage in lung were observed under light and electron-microscopy. Results:The levels of IL-1β and IL-1ra in blood were increased at 6 hours after I/R. The IL-1β level in injury group was obviously higher than that in the control group, while IL-1ra level was not increased significantly. However the IL-1ra level was increased obviously 6 hours after injury both in the injury and control group compared with their baseline values. The IL-1β level in lung perfusion liquid in injury group was also increased, while IL-1ra was not. The expression of IL-1β mRNA was higher in lung tissue after injury, and IL-1ra was not. The above-mentioned indexes in serum, lung perfusion liquid and lung tissue were all changed in certain degree. With the treatment of nonspecific blocking agent of PLA_2(such as chloroquine and terflazine), the blocking agent of platelet activating receptor such as SR27417A, the cyclic oxidase inhibitor such as mezolin or the oxidation resistant substancesuch as guaiac acid. The leukocytic aggregation and infiltration in lung were also decreased significantly. Conclusion: IL-1β and IL-1ra may be involved in the acute lung injury induced by gut I/R, and maybe related with the local activation of PLA_2.