Department of Anesthesiology, Taizhou First People's Hospital, Huangyan Hospital Affiliated to Wenzhou Medical University, Taizhou, Zhejiang, China.
Immun Inflamm Dis. 2022 Sep;10(9):e684. doi: 10.1002/iid3.684.
The lungs are extremely vulnerable to ischemia/reperfusion (I/R), which is characterized by intense inflammation, oxidative stress, alveolar damage, and vascular permeability. Parecoxib sodium (Pare) has been shown to exert protective effects against multiple I/R-induced tissue injuries. However, its role in I/R-induced lung injury remains unknown. This study aimed to reveal the roles and mechanisms of Pare in pulmonary I/R injury.
Sixty-six rats were randomly divided into three groups: The sham-operated group, the pulmonary I/R group, and the Pare-pretreated I/R group. Pare at 10 mg/kg or saline (vehicle control) were intraperitoneally administered to rats once per day for 5 consecutive days before ischemia. Serum and tissue samples were harvested following 2 h of reperfusion. The oxygenation index (OI) and alveolar-arterial oxygen partial pressure difference (PA-aO ) were analyzed. The levels or activities of malondialdehyde, superoxidase dismutase, catalase, glutathione peroxidase, intracellular reactive oxygen species, tumor necrosis factor-α, interleukin (IL)-6, and IL-8 were examined. The mitochondrial membrane potential was measured. The protein expression levels of the extracellular signal-regulated kinase (ERK), nuclear factor-κB (NF-κB) and their phosphorylated forms, and hypoxia-inducible factor-1α (HIF-1α) were detected. Histological changes were observed using hematoxylin and eosin staining. Moreover, the survival rate following pulmonary I/R injury was recorded daily.
Pare significantly increased the OI, decreased the PA-aO , increased the levels of antioxidants, while decreasing the levels of oxidants, and alleviated mitochondrial dysfunction and the histopathological damage induced by I/R. Furthermore, Pare inhibited the expression of proinflammatory cytokines, suppressed the activation of ERK and NF-κB, further increased HIF-1α expression, and significantly improved the rat survival rate.
Pare pretreatment attenuated lung I/R injury by inhibiting oxidative stress and the inflammatory response possibly via inhibiting the activation of the ERK/NF-κB pathway and further activating the HIF-1α pathway.
肺部极易受到缺血/再灌注（I/R）的影响，其特征为强烈的炎症、氧化应激、肺泡损伤和血管通透性增加。帕瑞昔布钠（Pare）已被证明可对多种 I/R 诱导的组织损伤发挥保护作用。然而，其在 I/R 诱导的肺损伤中的作用尚不清楚。本研究旨在揭示 Pare 在肺 I/R 损伤中的作用和机制。
66 只大鼠随机分为三组：假手术组、肺 I/R 组和 Pare 预处理 I/R 组。缺血前每天腹腔内给予 Pare10mg/kg 或生理盐水（载体对照），连续 5 天。再灌注 2 小时后采集血清和组织样本。分析氧合指数（OI）和肺泡-动脉血氧分压差（PA-aO ）。检测丙二醛、超氧化物歧化酶、过氧化氢酶、谷胱甘肽过氧化物酶、细胞内活性氧、肿瘤坏死因子-α、白细胞介素（IL）-6 和 IL-8 的水平或活性。测量线粒体膜电位。检测细胞外信号调节激酶（ERK）、核因子-κB（NF-κB）及其磷酸化形式和缺氧诱导因子-1α（HIF-1α）的蛋白表达水平。苏木精和伊红染色观察组织学变化。此外，每日记录肺 I/R 损伤后的生存率。
Pare 显著提高了 OI，降低了 PA-aO ，增加了抗氧化剂的水平，降低了氧化剂的水平，并缓解了 I/R 引起的线粒体功能障碍和组织病理学损伤。此外，Pare 抑制了促炎细胞因子的表达，抑制了 ERK 和 NF-κB 的激活，进一步增加了 HIF-1α的表达，并显著提高了大鼠的生存率。
Pare 预处理通过抑制氧化应激和炎症反应减轻肺 I/R 损伤，可能通过抑制 ERK/NF-κB 通路的激活并进一步激活 HIF-1α 通路。
