Lu Bai-Tao, Wang Ya-Jun, Wang Lei, Wu Di, Lin Yi-Lu, Xu Jia-Xi, Zhang Jia-Ning, Liu Bo-Wen, Liu Hui-Ying, Meng Huan, Gao Yang, Wang Hong-Liang, Kang Kai
Department of Critical Care Medicine, The First Affiliated Hospital of Harbin Medical University, No.23 Youzheng Street, Harbin, 150001, Heilongjiang Province, China.
Department of Pediatrics, The Sixth Affiliated Hospital of Harbin Medical University, Harbin, 150027, Heilongjiang Province, China.
Sci Rep. 2025 Apr 23;15(1):14004. doi: 10.1038/s41598-025-98740-3.
Shenfu injection (SFI) is a traditional Chinese medicine (TCM) for treating sepsis. The purpose of this study was to evaluate the protective effect of SFI on lipopolysaccharide (LPS)-induced liver injury in septic mice. The results showed that SFI intervention reduced liver/body weight and significantly improved the survival rate of septic mice. SFI could relieve the apoptosis of liver cells and ameliorate liver function in LPS-induced septic mice. SFI also diminished the serum and liver levels of the inflammatory factors IL-1β, IL-6, IL-18, IL-12, and TNF-α in a dose-dependent manner. SFI enhanced the mitochondrial membrane potential and alleviated the mitochondrial damage of liver in septic mice. Western blot revealed that the phosphorylation levels of IκB and NF-κB p65 increased significantly in the liver of LPS-induced septic mice. After SFI intervention, the phosphorylation levels of IκB and NF-κB p65 gradually recovered, especially at high concentration. SFI treatment reduced nuclear transduction, thus reducing transcriptional activity, which indicated that NF-κB p65 signal pathway might contribute to the anti-inflammatory and anti-apoptotic activities of SFI in the liver of LPS-induced septic mice. In addition, the metabolic profile of liver tissue in the model group was different from that in the control group, and SFI significantly regulated liver purine metabolism. These valuable findings suggested that SFI could improve mitochondrial function and mitigate inflammation and apoptosis, and thus alleviate LPS-induced liver injury in septic mice. SFI may be a promising drug to treat septic liver injury.
参附注射液（SFI）是一种用于治疗脓毒症的中药。本研究的目的是评估SFI对脂多糖（LPS）诱导的脓毒症小鼠肝损伤的保护作用。结果表明，SFI干预降低了肝/体重比，并显著提高了脓毒症小鼠的存活率。SFI可减轻LPS诱导的脓毒症小鼠肝细胞的凋亡并改善肝功能。SFI还以剂量依赖的方式降低了炎症因子IL-1β、IL-6、IL-18、IL-12和TNF-α的血清和肝脏水平。SFI增强了线粒体膜电位并减轻了脓毒症小鼠肝脏的线粒体损伤。蛋白质免疫印迹法显示，LPS诱导的脓毒症小鼠肝脏中IκB和NF-κB p65的磷酸化水平显著升高。SFI干预后，IκB和NF-κB p65的磷酸化水平逐渐恢复，尤其是在高浓度时。SFI处理减少了核转导，从而降低了转录活性，这表明NF-κB p65信号通路可能有助于SFI在LPS诱导的脓毒症小鼠肝脏中的抗炎和抗凋亡活性。此外，模型组肝脏组织的代谢谱与对照组不同，SFI显著调节肝脏嘌呤代谢。这些有价值的发现表明，SFI可以改善线粒体功能，减轻炎症和凋亡，从而减轻LPS诱导的脓毒症小鼠的肝损伤。SFI可能是一种治疗脓毒症肝损伤的有前景的药物。
