Department of Anesthesiology, Nanjing First Hospital, Nanjing Medical University, Jiangsu 210000, China; Department of Anesthesiology, Jiangning Hospital Affiliated to Nanjing Medical University, Jiangsu 211100, China.
Department of Anesthesiology, the First Affiliated Hospital of Naval Medical University, Shanghai 200433, China; Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Jiangsu 210093, China.
Mol Immunol. 2024 Apr;168:64-74. doi: 10.1016/j.molimm.2024.02.001. Epub 2024 Feb 29.
Septic lung injury is characterized by uncontrollable inflammatory infiltrations and acute onset bilateral hypoxemia. Evidence has emerged of the beneficial effect of hydrogen in acute lung injury (ALI), but the underlying mechanism is unclear. In this research, the recovery action of hydrogen on lipopolysaccharide (LPS)-induced ALI in mice and A549 cells was investigated. The 7-day survival rate and body weight of mice were measured after intraperitoneal injection of LPS. Lung function was determined by a whole body plethysmography (WBP) system using the indicators respiratory rate and enhanced pause. Hematoxylin and eosin (HE) staining confirmed the signs of pulmonary edema and inflammatory ooze. Reverse transcription-polymerase chain reaction (RT-PCR) quantification was used to detect the expression of inflammatory factors. Western blotting analysis evaluated the expression levels of involved proteins in the AMP-activated protein kinase (AMPK) pathway. The experimental results confirmed that hydrogen provided an essential solution to the dissipative effects of LPS on survival rate, weight loss and lung function. The LPS-stimulated inflammatory factors, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were also suppressed by hydrogen in A549 cells. Western blot analysis showed that hydrogen significantly upregulated the levels of phosphorylated AMPK (p-AMPK) and lowered the LPS-induced increased expression of dynamin-related protein 1 (Drp1) and Caspase3. These findings prove that hydrogen attenuated LPS-treated ALI by activating the AMPK pathway, supporting the feasibility of hydrogen treatment for sepsis.
脓毒症性肺损伤的特征为不可控性炎症浸润和急性双侧低氧血症。有证据表明，氢气对急性肺损伤（ALI）具有有益作用，但具体机制尚不清楚。本研究旨在探讨氢气对脂多糖（LPS）诱导的小鼠和 A549 细胞 ALI 的恢复作用。通过腹腔注射 LPS 后测量小鼠的 7 天存活率和体重，通过全身 plethysmography（WBP）系统测定呼吸频率和增强暂停等肺功能指标，对肺水肿和炎症渗出的特征进行苏木精和伊红（HE）染色确认。逆转录聚合酶链反应（RT-PCR）定量检测炎症因子的表达，Western blot 分析评估 AMP 激活蛋白激酶（AMPK）通路中涉及蛋白的表达水平。实验结果证实，氢气为 LPS 对存活率、体重减轻和肺功能的消散作用提供了重要的解决方案。氢气还抑制了 LPS 刺激的 A549 细胞中白细胞介素 6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素 1β（IL-1β）等炎症因子的表达。Western blot 分析表明，氢气显著上调磷酸化 AMPK（p-AMPK）的水平，并降低 LPS 诱导的动力相关蛋白 1（Drp1）和 Caspase3 表达增加。这些发现证明，氢气通过激活 AMPK 通路减轻 LPS 处理的 ALI，支持氢气治疗脓毒症的可行性。
