Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, China.
Basic Clin Pharmacol Toxicol. 2021 Jun;128(6):719-730. doi: 10.1111/bcpt.13561. Epub 2021 Feb 1.
The main causes of lung injury after cardiopulmonary bypass (CPB) are systemic inflammatory response syndrome (SIRS) and pulmonary ischaemia-reperfusion injury (IR-I). SIRS and IR-I are often initiated by a systemic inflammatory response. The present study investigated whether the annexin A1 (ANX-A1) peptidomimetic Ac2-26 by binding to formyl peptide receptors (FPRs) inhibit inflammatory cytokines and reduce lung injury after CPB. Male rats were randomized to the following five groups (n = 6, each): sham, exposed to pulmonary ischaemic-reperfusion (IR-I), IR-I plus Ac2-26, IR-I plus the FPR antagonist, BoC2 (N-tert-butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe) and IR-I plus Ac2-26 and BoC2. Treatment with Ac2-26 improved the oxygenation index, an effect blocked by BoC2. Histopathological analysis of the lung tissue revealed that the degree of lung injury was significantly less (P < 0.05) in the Ac2-26-treated rats compared to the other experimental groups exposed to IR-I. Ac2-26 treatment reduced the levels of the inflammatory cytokines TNF-α, IL-1β, ICAM-1 and NF-κB-p65 (P < 0.05) compared to the vehicle-treated group exposed to IR-I. In conclusion, the annexin A1 (ANX-A1) peptidomimetic Ac2-26 by binding to formyl peptide receptors inhibit inflammatory cytokines and reduce ischaemic-reperfusion lung injury after cardiopulmonary bypass.
体外循环（CPB）后肺损伤的主要原因是全身炎症反应综合征（SIRS）和肺缺血再灌注损伤（IR-I）。SIRS 和 IR-I 通常由全身炎症反应引发。本研究探讨了通过与甲酰肽受体（FPR）结合抑制炎症细胞因子并减少 CPB 后肺损伤的膜联蛋白 A1（ANX-A1）肽模拟物 Ac2-26 是否具有这种作用。雄性大鼠随机分为以下五组（每组 n=6）：假手术组、肺缺血再灌注组（IR-I 组）、IR-I 加 Ac2-26 组、IR-I 加 FPR 拮抗剂 Boc2[N-叔丁氧羰基-苯丙氨酰-亮氨酰-苯丙氨酰-亮氨酰]组和 IR-I 加 Ac2-26 和 Boc2 组。Ac2-26 治疗可改善氧合指数，Boc2 可阻断该作用。肺组织的组织病理学分析表明，与其他 IR-I 暴露的实验大鼠相比，Ac2-26 治疗的大鼠肺损伤程度显著降低（P<0.05）。与 IR-I 暴露的载体处理组相比，Ac2-26 治疗可降低 TNF-α、IL-1β、ICAM-1 和 NF-κB-p65 等炎症细胞因子的水平（P<0.05）。总之，通过与甲酰肽受体结合抑制炎症细胞因子并减少 CPB 后缺血再灌注肺损伤的膜联蛋白 A1（ANX-A1）肽模拟物 Ac2-26。
