Ping Kaixin, Yang Rongrong, Chen Huizhen, Xie Shaocheng, Xiang Yannan, Li Mengxin, Lu Yingzhi, Dong Jingquan
Jiangsu Key Laboratory of Marine Bioresources and Environment, Co-Innovation Center of Jiangsu Marine Bio-Industry Technology, Jiangsu Marine Pharmaceutical Resources Development Engineering Research Center, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, Jiangsu Ocean University, Lianyungang, 222005, China.
Institute of Neuroscience, Neurosurgery Department, The First People's Hospital of Lianyungang, Lianyungang, 222005, China.
Inflammation. 2025 Feb;48(1):42-60. doi: 10.1007/s10753-024-02041-2. Epub 2024 May 8.
Currently, treatment options for acute lung injury (ALI) are limited. Gypenoside XLIX (Gyp-XLIX) is known for its anti-inflammatory properties, but there is a lack of extensive research on its effects against ALI. This study induced ALI in mice through cecal ligation and puncture surgery and investigated the biological activity and potential mechanisms of Gypenoside XLIX (40 mg/kg) by intraperitoneal injection. The in vitro ALI model was established using mouse lung epithelial (MLE-12) cells stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP). Various methods, including Hematoxylin and Eosin (H&E) staining, biochemical assay kits, Quantitative Polymerase Chain Reaction (qPCR) analysis, Western blotting, Terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) assay, immunofluorescence, and flow cytometry, were employed for this research. The results indicated that pretreatment with Gypenoside XLIX significantly alleviated pathological damage in mouse lung tissues and reduced the expression levels of inflammatory factors. Additionally, Gypenoside XLIX inhibited ROS levels and NLRP3 inflammasome, possibly mediated by the Sirt1/Nrf2 signaling pathway. Moreover, Gypenoside XLIX significantly inhibited sepsis-induced lung cell apoptosis and excessive autophagy of mitochondria. Specifically, it suppressed mitochondrial pathway apoptosis and the Pink1/Parkin pathway of mitochondrial autophagy. These findings reveal the multifaceted effects of Gypenoside XLIX in anti-inflammatory, antioxidative, and inhibition of cell apoptosis and autophagy. This provides strong support for its therapeutic potential in sepsis-related lung injuries.
目前，急性肺损伤（ALI）的治疗选择有限。绞股蓝皂苷XLIX（Gyp-XLIX）以其抗炎特性而闻名，但对其抗ALI作用缺乏广泛研究。本研究通过盲肠结扎和穿刺手术诱导小鼠发生ALI，并通过腹腔注射研究绞股蓝皂苷XLIX（40mg/kg）的生物学活性和潜在机制。使用脂多糖（LPS）和三磷酸腺苷（ATP）刺激的小鼠肺上皮（MLE-12）细胞建立体外ALI模型。本研究采用了多种方法，包括苏木精和伊红（H&E）染色、生化检测试剂盒、定量聚合酶链反应（qPCR）分析、蛋白质免疫印迹法、末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）检测、免疫荧光和流式细胞术。结果表明，绞股蓝皂苷XLIX预处理可显著减轻小鼠肺组织的病理损伤，并降低炎症因子的表达水平。此外，绞股蓝皂苷XLIX抑制ROS水平和NLRP3炎性小体，可能由Sirtl/Nrf2信号通路介导。此外，绞股蓝皂苷XLIX显著抑制脓毒症诱导的肺细胞凋亡和线粒体过度自噬。具体而言，它抑制线粒体途径凋亡和线粒体自噬的Pink1/Parkin途径。这些发现揭示了绞股蓝皂苷XLIX在抗炎、抗氧化以及抑制细胞凋亡和自噬方面的多方面作用。这为其在脓毒症相关肺损伤中的治疗潜力提供了有力支持。
