Zhang Song, Yue Yan, Liu Jing, Zhi Lijia, Zhang Li, Zhang Kaichen, Ding Peng, Gao Peiyang, Long Kunlan
Department of Critical Care Medicine, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Nursing Department, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
J Thorac Dis. 2023 Jun 30;15(6):3409-3420. doi: 10.21037/jtd-23-367. Epub 2023 Jun 16.
Acute respiratory distress syndrome (ARDS) is a common life-threatening critical illness with high mortality. Fusu mixture (FSM) can improve the mechanical ventilation in ARDS patients. However, the detailed pharmacological mechanisms and active substances of FSM are still unclear. This study aimed to explore the potential pharmacological mechanisms of FSM for treating ARDS and its chemical compositions.
A lipopolysaccharide (LPS)-induced ARDS mouse model was established, and the mice subsequently received FSM (50 mg/kg) orally for 5 days. Then, the blood samples and lung tissues were collected. Enzyme-linked immunosorbent assay (ELISA) was used to determine the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in serum, and histopathology examinations were applied to analyze the inflammatory response of lung tissues in ARDS mice. In addition, protein expressions of aquaporin 5 (AQP-5), surfactant-associated protein C (SP-C), and Notch1 were detected by western blot assays and immunohistochemical (IHC) examination. In addition, the chemical compositions of FSM were analyzed by high performance liquid chromatography (HPLC), using standard reference agents.
After LPS induction, the serum levels of IL-6 and TNF-α in ARDS mice were significantly increased (P<0.01, Control), and FSM significantly reduced these 2 pro-inflammatory cytokines (IL-6 and TNF-α) compared to the model mice (P<0.01). Histopathology examinations showed FSM significantly attenuated the inflammatory responses in lung tissues. Furthermore, after FSM treatment, the SP-C and AQP-5 were significantly increased, compared to the Model mice (P<0.01), and FSM also up-regulated the Notch1 expressions in lung tissues of ARDS mice (P<0.001, Model).
Collectively, it is suggested that FSM alleviates inflammatory reactions and promotes the proliferation of alveolar epithelial cells in LPS-induced ARDS mice via regulation of SP-C, AQP-5, and Notch1 in lung tissues.
急性呼吸窘迫综合征（ARDS）是一种常见的危及生命的危重病，死亡率很高。伏苏合剂（FSM）可改善ARDS患者的机械通气。然而，FSM的详细药理机制和活性成分仍不清楚。本研究旨在探讨FSM治疗ARDS的潜在药理机制及其化学成分。
建立脂多糖（LPS）诱导的ARDS小鼠模型，随后小鼠口服FSM（50mg/kg），持续5天。然后，采集血液样本和肺组织。采用酶联免疫吸附测定（ELISA）法测定血清中肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）水平，并应用组织病理学检查分析ARDS小鼠肺组织的炎症反应。此外，通过蛋白质印迹分析和免疫组织化学（IHC）检查检测水通道蛋白5（AQP-5）、表面活性物质相关蛋白C（SP-C）和Notch1的蛋白表达。另外，采用高效液相色谱（HPLC）法，使用标准对照品分析FSM的化学成分。
LPS诱导后，ARDS小鼠血清中IL-6和TNF-α水平显著升高（P<0.01，与对照组相比），与模型小鼠相比，FSM显著降低了这两种促炎细胞因子（IL-6和TNF-α）（P<0.01）。组织病理学检查显示，FSM显著减轻了肺组织的炎症反应。此外，与模型小鼠相比，FSM治疗后，SP-C和AQP-5显著增加（P<0.01），FSM还上调了ARDS小鼠肺组织中Notch1的表达（P<0.001，与模型组相比）。
总体而言，提示FSM通过调节肺组织中的SP-C、AQP-5和Notch1，减轻LPS诱导的ARDS小鼠的炎症反应，促进肺泡上皮细胞增殖。
