医学分子生物学杂志 ›› 2022, Vol. 19 ›› Issue (6): 484-489.doi: 10.3870/j.issn.1672-8009.2022.06.008

• 论著 • 上一篇    下一篇

罗哌卡因通过 HMGB1 / NF-κB 通路减轻 LPS 诱导的小鼠急性 肺损伤 

  

  1. 1东营市东营区人民医院麻醉科 山东省东营市, 257000  2东营市东营区人民医院妇科 山东省东营市, 257000  3胜利油田中心医院疼痛科 山东省东营市, 257000
  • 出版日期:2022-11-30 发布日期:2023-02-14

Ropivacaine Alleviates LPS Induced Acute Lung Injury in Mice via HMGB1 / NF-κB Pathway

  1. 1Department of Anesthesiology, Dongying District People ’ s Hospital, Dongying, Shandong, 257000, China  2Department of Gynecology, Dongying District People’s Hospital, Dongying, Shandong, 257000, China  3Department of Pain, Shengli Oilfield Central Hospital, Dongying, Shandong, 257000, China 
  • Online:2022-11-30 Published:2023-02-14

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摘要： 目的 探讨罗哌卡因 ( ropivacaine, Rop) 对脂多糖 ( lipopolysaccharide, LPS) 诱导的小鼠急性 肺损伤 (acute lung injury, ALI) 的作用及其机制。 方法 气管内滴注 LPS 诱导肺损伤小鼠模型, 并将小鼠 随机分为 6 组: 对照组、 LPS 组、 罗哌卡因 0. 25、 0. 5、 1 μmol / L 组和右美托咪定 (dexmedetomidine, Dex) 100 μg / kg 组。 Hematoxylin-eosin (H&E) 染色评估肺组织的组织病理学变化; ELISA 法测定肺组织中髓过 氧化物酶 (myeloperoxidase, MPO)、 丙二醛 ( malondialdehyde, MDA)、 超氧化物歧化酶 ( superoxide dismutase, SOD) 和谷胱甘肽过氧化物酶 ( glutathione peroxidase, GSH-Px) 的活性; 检测血清中 IL-6、 IL-1β 和肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α) 的表达; Western 印迹检测 HMGB1 / NF-κB 通路相关蛋 白的表达。 结果 与对照组比较, LPS 诱导肺泡外膜增厚、 出血和肺水肿; 肺损伤评分和肺含水量增加; MPO 和 MDA 活性增加, SOD 和 GSH-Px 水平降低; IL-6、 IL-1β 和 TNF-α 水平升高; HMGB1 蛋白和 NF-κB P65 磷酸化水平升高, 有显著性差异 (P< 0. 05)。 与 LPS 组比较, 罗哌卡因 0. 5、 1 μmol / L 组小鼠肺损伤 程度明显减轻; MPO 和 MDA 活性降低, SOD 和 GSH-Px 水平升高; IL-6、 IL-1β 和 TNF-α 水平降低; HMGB1 蛋白和 NF-κB P65 磷酸化水平降低, 有显著性差异 (P< 0. 05)。 结论 罗哌卡因通过抑制 HMGB1 / NF-κB 通路, 有效减弱了 LPS 引起的肺组织损伤。

关键词: 罗哌卡因, 肺损伤, 脂多糖, NF-κB

Abstract: Objective To investigate the effect and mechanism of ropivacaine (Rop) on lipopolysaccharide (LPS) -induced acute lung injury (ALI) in mice. Methods Mice with lung injury induced by endotracheal infusion of LPS were randomly divided into 6 groups: the control group, the LPS group, the Rop 0. 25 μmol / L group, the Rop 0. 5 μmol / L group, the Rop 1 μmol / L group and the dexmedetomidine ( Dex) 100 μg / kg group. Hematoxylin-eosin ( H&E) staining was used to evaluate histopathological changes of the lung tissues. The activities of myeloperoxidase (MPO) and malondialdehyde (MDA) in lung tissues of mice were determined by the colorimetric method. The levels of superoxide dismutase ( SOD) and glutathione peroxidase ( GSH-Px) in lung tissues, and the expression levels of interleukin ( IL) -6, IL-1β and tumor necrosis factor (TNF) -α in serum were assayed by ELISA. The expression levels of HMGB1 / NF-κB path- way related proteins were detected by Western blotting. Results The treatment of LPS induced the occurrence of hemorrhage and pulmonary edema in mice, and the thickening of alveolar membrane in lung tissues. The lung injury score and the water content in the lung tissues were increased in the LPS group when compared with the control group. The activities of MPO and MDA, the levels of IL-6, IL-1β and TNF-α in serum were increased in the LPS group, while the levels of SOD and GSH-Px were decreased. The expression level of HMGB1 protein was increased and the phosphorylation of NF-κB P65 were upregulated in the LPS group (P<0. 05). Compared with LPS group, the degree of lung injury in mice was significantly decreased, the activities of MPO and MDA, the levels of IL-6, IL-1β and TNF-α in serum were decreased, while the levels of SOD and GSH-Px were increased after Rop treatment. The expression level of HMGB1 protein was decreased and the phosphorylation of NF-κB P65 was downregulated in the Rop 0. 5 and 1 μmol / L groups (P<0. 05). Conclusion Rop effectively attenuates the LPS-induced lung injury by inhibiting HMGB1 / NF-κB pathway.

Key words: ropivacaine, lung injury, lipopolysaccharide, NF-κB 

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