Zhang Lei, Zhang Guangyuan, Mao Weipu, Sun Si, Tao Shuchun, Gao Yue, Zhang Nieke, Jiang Guiya, Chen Ming, Lu Xun, Chen Shuqiu
Department of Urology, Zhongda Hospital, Southeast University, Nanjing, PR China.
Institute of Urology, Surgical Research Center, School of Medicine, Southeast University, Nanjing, PR China.
Ren Fail. 2025 Dec;47(1):2483986. doi: 10.1080/0886022X.2025.2483986. Epub 2025 Mar 27.
Xuebijing (XBJ) injection has been used to treat sepsis. However, the effect and mechanism of XBJ injection in the treatment of septic acute kidney injury (AKI) is unknown. This study aimed to explore the therapeutic effect of XBJ injection on septic AKI and elucidate its possible mechanisms.
Network pharmacological analysis was conducted using databases of GeneCards, TCMSP, SwissTargetPrediction and STRING. , a septic AKI model was established in C57BL/6 mice by cecal ligation and puncture (CLP). The groups were Sham, XBJ, CLP, and CLP + XBJ (10 mL/kg IV) ( = 5). Tubular damage, renal function, and levels of inflammation and apoptosis in the kidneys were evaluated. model was lipopolysaccharide (LPS, 100 μg/mL) stimulated HK-2 cells. The groups were PBS, XBJ, LPS, and LPS + XBJ (XBJ injected at 10 dilutions). Cell viability, apoptosis, inflammation, mitochondrial function and, endoplasmic reticulum (ER) stress were also assessed.
Network pharmacological analysis identified Toll like receptor 4 (TLR4) as the core gene in XBJ against septic AKI, and the inflammatory response was the most enriched pathway. XBJ treatment significantly alleviated tubular damage in CLP mice by down-regulating serum creatinine (SCr), blood urea nitrogen (BUN), kidney injury molecule 1 (KIM1), and neutrophil gelatinase-associated lipocalin (NGAL). Furthermore, both and experiments demonstrated that XBJ treatment could inhibit apoptosis, inflammation, mitochondrial dysfunction, and ER stress TLR4/MyD88/NF-κB axis.
This study indicates that XBJ injection is a promising drug for the treatment of septic AKI.
血必净（XBJ）注射液已用于治疗脓毒症。然而，XBJ注射液治疗脓毒症急性肾损伤（AKI）的效果和机制尚不清楚。本研究旨在探讨XBJ注射液对脓毒症AKI的治疗作用并阐明其可能的机制。
利用GeneCards、TCMSP、SwissTargetPrediction和STRING数据库进行网络药理学分析。通过盲肠结扎和穿刺（CLP）在C57BL/6小鼠中建立脓毒症AKI模型。分组为假手术组、XBJ组、CLP组和CLP+XBJ组（静脉注射10 mL/kg）（每组n=5）。评估肾小管损伤、肾功能以及肾脏中的炎症和凋亡水平。体外模型为脂多糖（LPS，100μg/mL）刺激的HK-2细胞。分组为PBS组、XBJ组、LPS组和LPS+XBJ组（XBJ以10种稀释度注射）。还评估了细胞活力、凋亡、炎症、线粒体功能和内质网（ER）应激。
网络药理学分析确定Toll样受体4（TLR4）是XBJ治疗脓毒症AKI的核心基因，炎症反应是最富集的通路。XBJ治疗通过下调血清肌酐（SCr）、血尿素氮（BUN）、肾损伤分子1（KIM1）和中性粒细胞明胶酶相关脂质运载蛋白（NGAL）显著减轻CLP小鼠的肾小管损伤。此外，体内和体外实验均表明，XBJ治疗可通过TLR4/MyD88/NF-κB轴抑制凋亡、炎症、线粒体功能障碍和ER应激。
本研究表明，XBJ注射液是治疗脓毒症AKI的一种有前景的药物。
