Anesthesiology Department, The Second Affiliated Hospital of Harbin Medical University, 246 Xuefu Road, Nangang District, Harbin 150000, China.
Department of ICU, The Tumor Hospital of Harbin Medical University, 150 Haping Road, Harbin 150081, China.
Biomed Pharmacother. 2019 Sep;117:109194. doi: 10.1016/j.biopha.2019.109194. Epub 2019 Jul 4.
Lung ischemia-reperfusion injury (LIRI) is a major complication after lung transplantation. Annexin A1 (AnxA1) ameliorates inflammation in various injured organs. This study aimed to determine the effects and mechanism of AnxA1 on LIRI after lung transplantation.
Thirty-two rats were randomized into sham, saline, Ac2-26 and Ac2-26/L groups. Rats in the saline, Ac2-26 and Ac2-26/L groups underwent left lung transplantation and received saline, Ac2-26, and Ac2-26/L-NIO, respectively. After 24 h of reperfusion, serum and transplanted lung tissues were examined.
The partial pressure of oxygen (PaO) was increased in the Ac2-26 group compared to that in the saline group but was decreased by L-NIO treatment. In the Ac2-26 group, the wet-to-dry (W/D) weight ratios, total protein concentrations, proinflammatory factors and inducible nitric oxide synthase levels were notably decreased, but the concentrations of anti-inflammatory factors and endothelial nitric oxide synthase levels were significantly increased. Ac2-26 attenuated histological injury and cell apoptosis, and this improvement was reversed by L-NIO.
Ac2-26 reduced LIRI and improved alveoli-capillary permeability by inhibiting oxygen stress, inflammation and apoptosis. The protective effect of Ac2-26 on LIRI largely depended on the endothelial nitric oxide synthase pathway.
肺缺血再灌注损伤（LIRI）是肺移植后的主要并发症。膜联蛋白 A1（AnxA1）可改善各种受损器官的炎症。本研究旨在确定 AnxA1 对肺移植后 LIRI 的影响和机制。
32 只大鼠随机分为假手术组、盐水组、Ac2-26 组和 Ac2-26/L 组。盐水组、Ac2-26 组和 Ac2-26/L 组大鼠接受左肺移植，分别给予生理盐水、Ac2-26 和 Ac2-26/L-NIO。再灌注 24 小时后，检测血清和移植肺组织。
与盐水组相比，Ac2-26 组的氧分压（PaO）升高，但 L-NIO 处理后降低。Ac2-26 组湿重/干重（W/D）比值、总蛋白浓度、促炎因子和诱导型一氧化氮合酶水平显著降低，抗炎因子和内皮型一氧化氮合酶水平显著升高。Ac2-26 减轻了组织学损伤和细胞凋亡，而 L-NIO 逆转了这种改善。
Ac2-26 通过抑制氧应激、炎症和细胞凋亡减轻 LIRI 并改善肺泡毛细血管通透性。Ac2-26 对 LIRI 的保护作用在很大程度上取决于内皮型一氧化氮合酶途径。
