Department of Cardiovascular Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
J Surg Res. 2024 Sep;301:324-335. doi: 10.1016/j.jss.2024.06.009. Epub 2024 Jul 15.
Cardiopulmonary bypass (CPB) leads to severe inflammation and lung injury. Our previous study showed that Ac2-26 (an active n-terminal peptide of Annexin A1) can reduce acute lung injury. The aim of this study was to evaluate the effect of Ac2-26 on lung injury in CPB rats.
Forty rats were randomly divided into the sham, CPB, Ac, Ac/serine/threonine kinase 1 (AKT1), and Ac/ glycogen synthase kinase (GSK)-3β groups. The rats in the sham group only received anesthesia, intubation, and cannulation. The rats in the other 4 groups received the standard CPB procedure. The rats in the CPB, Ac, Ac/AKT1, and Ac/GSK3β groups were immediately injected with saline, Ac2-26 (1 mg/kg), Ac2-26 combined with short hairpin RNA (AKT1), or Ac2-26 combined with a GSK3β inhibitor after CPB. At 12 h after the end of CPB, the PaO/ fraction of inspired oxygen ratio, wet/dry weight ratio and protein content in the bronchoalveolar lavage fluid (BALF) were recorded. The numbers of macrophages and neutrophils in the BALF and blood were determined. Cytokine levels in the blood and BALF were investigated. Lung tissue histology and apoptosis were estimated. The expression of nuclear factor kappa- B, AKT1, GSK3β, endothelial nitric oxide synthase and apoptosis-related proteins was analyzed. The survival of all the rats was recorded.
Compared with the rats in the sham group, all the parameters examined worsened in the rats that received CPB. Compared with those in the CPB group, Ac2-26 significantly improved pulmonary capillary permeability, reduced cytokine levels, and decreased histological scores and apoptosis. The protective effect of Ac2-26 on lung injury was significantly reversed by AKT1 short hairpin RNA or a GSK3β inhibitor.
Ac2-26 significantly reduced lung injury and inflammation after CPB. The protective effect of Ac2-26 mainly depended on the AKT1/GSK3β/endothelial nitric oxide synthase pathway.
体外循环（CPB）会导致严重的炎症和肺损伤。我们之前的研究表明，Ac2-26（ Annexin A1 的活性 N 端肽）可以减轻急性肺损伤。本研究旨在评估 Ac2-26 对 CPB 大鼠肺损伤的影响。
40 只大鼠随机分为假手术组、CPB 组、Ac 组、Ac/丝氨酸苏氨酸激酶 1（AKT1）组和 Ac/糖原合成酶激酶（GSK）-3β组。假手术组大鼠仅接受麻醉、插管和置管。其余 4 组大鼠接受标准 CPB 程序。CPB 组、Ac 组、Ac/AKT1 组和 Ac/GSK3β 组大鼠在 CPB 后立即注射生理盐水、Ac2-26（1mg/kg）、Ac2-26 与短发夹 RNA（AKT1）、或 Ac2-26 与 GSK3β 抑制剂。CPB 结束后 12 小时，记录 PaO/FiO2 比值、支气管肺泡灌洗液（BALF）湿/干重比和蛋白含量。测定 BALF 和血液中巨噬细胞和中性粒细胞的数量。检测血液和 BALF 中的细胞因子水平。评估肺组织病理学和细胞凋亡。分析核因子 kappa-B、AKT1、GSK3β、内皮型一氧化氮合酶和凋亡相关蛋白的表达。记录所有大鼠的存活情况。
与假手术组大鼠相比，接受 CPB 的大鼠所有检查参数均恶化。与 CPB 组相比，Ac2-26 显著改善肺毛细血管通透性，降低细胞因子水平，降低组织学评分和细胞凋亡。AKT1 短发夹 RNA 或 GSK3β 抑制剂显著逆转 Ac2-26 对肺损伤的保护作用。
Ac2-26 显著减轻 CPB 后肺损伤和炎症。Ac2-26 的保护作用主要依赖于 AKT1/GSK3β/内皮型一氧化氮合酶通路。
