Department of Anesthesiology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, No.725, South Wanping Road, Xuhui District, Shanghai 200032, China.
Department of Anesthesiology, Peking University Third Hospital, No. 49, North Garden Street, Haidian District, Beijing 100191, China.
Int Immunopharmacol. 2023 May;118:110082. doi: 10.1016/j.intimp.2023.110082. Epub 2023 Mar 28.
Sepsis-associated acute lung injury remains to be a major cause of morbidity and mortality worldwide, and there is a lack of effective therapeutic drugs. Curdione, an activeingredient of Curcuma zedoary, a traditional Chinese medicine (TCM), possesses a variety of pharmacological actions, such as anti-inflammatory, antioxidant and inhibition of platelet aggregation. However, whether curdione protects against sepsis-induced lung injury is still undetermined. In this study, we investigated the effects of curdione on sepsis-induced lung injury. Cecal ligation and puncture (CLP) surgery was performed in mice to establish a model of sepsis. Twenty-four hours after CLP, bronchoalveolar lavage fluid (BALF) and lung tissue samples were harvested for investigation. The protective effects of curdione on acute lung injury and potential mechanisms were explored by detecting pathological sections, exudative proteins, oxidative responses, inflammatory factors, platelet activation, neutrophil infiltration, and neutrophil extracellular trap (NET) formation in the lung and were further verified in vitro. We showed that treatment with curdione clearly relieved histopathological changes, reduced inflammatory cytokine elevation and total protein concentrations in BALF, and decreased oxidative stress responses in lung tissues. In addition, curdione inhibited platelet activation, further blocking the interaction between platelets and neutrophils. Finally, neutrophil infiltration and NET formation was also reduced in mice treated with curdione. In conclusion, curdione alleviates sepsis-induced lung injury by inhibiting platelet-mediated neutrophil recruitment, infiltration, and NET formation as well as its anti-inflammatory and antioxidant properties. Curdione has great therapeutic potential in sepsis.
脓毒症相关性急性肺损伤仍然是全球发病率和死亡率的主要原因，并且缺乏有效的治疗药物。莪术酮是莪术的一种活性成分，莪术是一种中药，具有多种药理作用，如抗炎、抗氧化和抑制血小板聚集。然而，莪术酮是否对脓毒症引起的肺损伤具有保护作用仍不确定。在这项研究中，我们研究了莪术酮对脓毒症引起的肺损伤的作用。在小鼠中进行盲肠结扎和穿孔（CLP）手术以建立脓毒症模型。CLP 后 24 小时，采集支气管肺泡灌洗液（BALF）和肺组织样本进行研究。通过检测肺组织中的病理切片、渗出性蛋白、氧化反应、炎症因子、血小板激活、中性粒细胞浸润和中性粒细胞胞外陷阱（NET）形成，探讨了莪术酮对急性肺损伤的保护作用及其潜在机制，并在体外进行了验证。我们发现，莪术酮治疗明显缓解了组织病理学变化，降低了 BALF 中炎症细胞因子的升高和总蛋白浓度，并降低了肺组织中的氧化应激反应。此外，莪术酮抑制了血小板的激活，从而进一步阻断了血小板与中性粒细胞之间的相互作用。最后，莪术酮治疗还减少了小鼠中性粒细胞的浸润和 NET 的形成。总之，莪术酮通过抑制血小板介导的中性粒细胞募集、浸润和 NET 形成以及其抗炎和抗氧化特性，减轻脓毒症引起的肺损伤。莪术酮在脓毒症中有很大的治疗潜力。
