Department of Emergency Medicine, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210002, PR China; Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, PR China; Department of Emergency Medicine, Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou, Jiangsu Province 221000, PR China.
Department of Emergency Medicine, Jinling Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210002, PR China; Department of Emergency Medicine, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, PR China; Department of Emergency Medicine, the Affiliated Hospital of Xuzhou Medical University, Xuzhou 221002, PR China.
Phytomedicine. 2024 Jul;129:155627. doi: 10.1016/j.phymed.2024.155627. Epub 2024 Apr 17.
Sepsis is a life-threatening organ dysfunction caused by an exaggerated response to infection. In the lungs, one of the most susceptible organs, this can manifest as acute respiratory distress syndrome (ARDS). Shenfu (SF) injection is a prominent traditional Chinese medicine used to treat sepsis. However, the exact mechanism of its action has rarely been reported in the literature.
In the present study, we detected the protective effect of SF injection on sepsis-induced ARDS and explored its underlying mechanism.
We investigated the potential targets and regulatory mechanisms of SF injections using a combination of network pharmacology and RNA sequencing. This study was conducted both in vivo and in vitro using a mouse model of ARDS and lipopolysaccharide (LPS)-stimulated MLE-12 cells, respectively.
The results showed that SF injection could effectively inhibit inflammation, oxidative stress, and apoptosis to alleviate LPS-induced ARDS. SF inhibited the PI3K-AKT pathway, which controls autophagy and apoptosis. Subsequently, MLE-12 cells were treated with 3-methyladenine to assess its effects on autophagy and apoptosis. Additional experiments were conducted by adding rapamycin, an mTOR antagonist, or SC79, an AKT agonist, to investigate the effects of SF injection on autophagy, apoptosis, and the PI3K-AKT pathway.
Overall, we found that SF administration could enhance autophagic activity, reduce apoptosis, suppress inflammatory responses and oxidative stress, and inhibit the PI3K-AKT pathway, thus ameliorating sepsis-induced ARDS.
脓毒症是一种由感染引起的危及生命的器官功能障碍，其特征是对感染的过度反应。在肺部，这是最易受影响的器官之一，这种情况可能表现为急性呼吸窘迫综合征（ARDS）。参附（SF）注射液是一种用于治疗脓毒症的中药。然而，其作用机制在文献中鲜有报道。
本研究旨在检测 SF 注射液对脓毒症诱导的 ARDS 的保护作用，并探讨其潜在机制。
我们结合网络药理学和 RNA 测序技术，研究了 SF 注射液的潜在靶点和调控机制。本研究分别在 ARDS 小鼠模型和脂多糖（LPS）刺激的 MLE-12 细胞中进行了体内和体外实验。
结果表明，SF 注射液能有效抑制炎症、氧化应激和凋亡，从而缓解 LPS 诱导的 ARDS。SF 抑制了 PI3K-AKT 通路，该通路控制自噬和凋亡。随后，用 3-甲基腺嘌呤处理 MLE-12 细胞，以评估其对自噬和凋亡的影响。通过添加雷帕霉素（mTOR 拮抗剂）或 SC79（AKT 激动剂），进一步研究 SF 注射液对自噬、凋亡和 PI3K-AKT 通路的影响。
综上所述，我们发现 SF 给药可以增强自噬活性，减少凋亡，抑制炎症反应和氧化应激，抑制 PI3K-AKT 通路，从而改善脓毒症诱导的 ARDS。
