Xuebijing injection alleviates septic acute kidney injury by modulating inflammation, mitochondrial dysfunction, and endoplasmic reticulum stress.

IF 3 3区 医学 Q1 UROLOGY & NEPHROLOGY
Renal Failure Pub Date : 2025-12-01 Epub Date: 2025-03-27 DOI:10.1080/0886022X.2025.2483986
Lei Zhang, Guangyuan Zhang, Weipu Mao, Si Sun, Shuchun Tao, Yue Gao, Nieke Zhang, Guiya Jiang, Ming Chen, Xun Lu, Shuqiu Chen
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引用次数: 0

Abstract

Background: 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.

Methods: Network pharmacological analysis was conducted using databases of GeneCards, TCMSP, SwissTargetPrediction and STRING. In vivo, 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) (n = 5). Tubular damage, renal function, and levels of inflammation and apoptosis in the kidneys were evaluated. In vitro 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.

Results: 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 in vivo and in vitro experiments demonstrated that XBJ treatment could inhibit apoptosis, inflammation, mitochondrial dysfunction, and ER stress via TLR4/MyD88/NF-κB axis.

Conclusion: This study indicates that XBJ injection is a promising drug for the treatment of septic AKI.

血必净注射液通过调节炎症、线粒体功能障碍和内质网应激减轻脓毒性急性肾损伤。
背景:血必静注射液已被用于治疗脓毒症。然而,XBJ注射液治疗脓毒性急性肾损伤(AKI)的作用和机制尚不清楚。本研究旨在探讨XBJ注射液对脓毒性AKI的治疗作用,并阐明其可能的机制。方法:使用GeneCards、TCMSP、SwissTargetPrediction和STRING数据库进行网络药理分析。在体内,采用盲肠结扎穿刺法(CLP)建立C57BL/6小鼠脓毒性AKI模型。各组分别为Sham、XBJ、CLP、CLP + XBJ (10 mL/kg IV) (n = 5)。评估肾小管损伤、肾功能、炎症和凋亡水平。体外模型采用脂多糖(LPS, 100 μg/mL)刺激HK-2细胞。实验组为PBS、XBJ、LPS、LPS + XBJ (XBJ按10倍稀释注射)。细胞活力、凋亡、炎症、线粒体功能和内质网(ER)应激也被评估。结果:网络药理学分析发现Toll样受体4 (TLR4)是XBJ抗脓毒性AKI的核心基因,炎症反应是最富集的途径。XBJ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钙蛋白(NGAL),显著减轻CLP小鼠肾小管损伤。此外,体内和体外实验均表明,XBJ可通过TLR4/MyD88/NF-κB轴抑制细胞凋亡、炎症、线粒体功能障碍和内质网应激。结论:XBJ注射液是治疗感染性AKI的一种有前景的药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Renal Failure
Renal Failure 医学-泌尿学与肾脏学
CiteScore
3.90
自引率
13.30%
发文量
374
审稿时长
1 months
期刊介绍: Renal Failure primarily concentrates on acute renal injury and its consequence, but also addresses advances in the fields of chronic renal failure, hypertension, and renal transplantation. Bringing together both clinical and experimental aspects of renal failure, this publication presents timely, practical information on pathology and pathophysiology of acute renal failure; nephrotoxicity of drugs and other substances; prevention, treatment, and therapy of renal failure; renal failure in association with transplantation, hypertension, and diabetes mellitus.
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