Annexin A1对婴幼儿体外循环术后急性肺损伤的保护研究

For infant congenial heart disease, acute lung injury is one of the most common and serious complications after cardiopulmonary bypass. Various studies indicate acute lung injury is closely associated with the imbalance between pro-inflammatory and anti-inflammation response. Annexin A1, as an anti-inflammation protein, was indicated to protect organs’ function by inhibiting inflammation response in a great many of animal models. However, no study was reported on the mechanism of Annexin A1 in acute lung injury induced by cardiopulmonary bypass(CPB). Our previous studies showed Annexin A1 was involved with CPB. Based on above studies , we speculate a lack of Annexin A1 expression might be strongly linked with acute lung injury after CPB. Here we combine the clinical study and neonatal pig acute lung injury model by CPB, utilize molecular techniques and drug treatment(Methylprednisolone Sodium Succinate for injection, Anx-12–26, nonselective FMP receptorantigonist Boc 2, investigate the function of Annexin A1 in preventing and treating acute lung injury during CPB and initially explore the mechanism of Annexin A1 protection of lung. Hope in the future Annexin A1 might be targeted as new drug development and a feasible means of preventing or treating acute lung injury after CPB can be found.

急性肺损伤是婴幼儿先天性心脏病体外循环术后早期最常见、最严重的并发症之一，各种研究提示急性肺损伤与体外循环术后炎症反应和抗炎反应严重失衡密切相关。Annexin A1作为一种重要的抗炎分子，在多种动物模型上被证实有抑制炎症反应, 保护脏器作用，但Annexin A1在体外循环术后急性肺损伤发生过程中的保护作用机制尚不明了。前期研究提示Annexin A1参与体外循环术后的抗炎作用，推测体外循环后急性肺损伤与Annexin A1表达不足有关，本研究将临床和动物实验相结合，利用分子生物学技术和注射用甲泼尼龙琥珀酸钠，Acetyl-2-26或非选择性FMP受体拮抗剂Boc 2药物处理，明确Annexin A1在体外循环术中预防肺损伤的作用，并探索Annexin A1保护肺的机制，为先天性心脏病婴幼儿体外循环术急性肺损伤的治疗寻找可行的预防和治疗方法。

急性肺损伤是婴幼儿先天性心脏病体外循环术后早期最常见、最严重的并发症之一，各种研究提示急性肺损伤与体外循环术后炎症反应和抗炎反应严重失衡密切相关。表皮生长因子受体EGFR在炎症反应的发生发展过程中也起到重要作用。表皮生长因子EGFR参与了体外循环导致的急性肺损伤的过程，本课题通过建立动物体外循环模型，结合细胞生物学、蛋白质生物学等方法与技术，对EGFR参与体外循环急性肺损伤的机制进行了初步研究。首先采用兔自体血预冲，实现主动脉完全阻断，心脏停跳，改良了经右心房引流，主动脉灌注，有血预充的兔CPB急性肺损伤模型，进一步优化了 CPB建模方案；通过ELISA、Westernblot、免疫荧光等技术，我们发现特异性抑制表皮生长因子的表达，可减少炎症因子的生成和释放。综上所述，本研究明确EGFR在参与体外循环术中肺损伤发生，为探讨EGFR导致急性肺损伤的机制奠定了坚实的研究基础，同时为先天性心脏病婴幼儿体外循环术急性肺损伤的治疗提出了新的治疗思路。项目资助发表核心论文1篇，后续文章正在撰写中。培养硕士生1名，已经取得硕士学位。