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基于PK-PD和抗体芯片技术的芪归银汤对左氧氟沙星抗多重耐药感染的增敏机制研究

Mechanism of Qiguiyin Decoction Sensitizing Levofloxacin Against Multidrug-Resistant Infection Based on PK-PD and Antibody Chip Technology.

作者信息

Li Yanling, Ji Li, Liu Tian, Xu Guang, Wang Kaihe, Mu Leixin, Guo Yuying, Ma Qun

机构信息

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 102488, People's Republic of China.

出版信息

Infect Drug Resist. 2024 May 27;17:2089-2098. doi: 10.2147/IDR.S455114. eCollection 2024.

Abstract

BACKGROUND

Qiguiyin decoction (QGYD) is a traditional Chinese medicine (TCM) and its combined application with levofloxacin (LVFX) has been confirmed effective in the clinical treatment of multidrug-resistant (MDR PA) infection. This study investigated the therapeutic effect and possible mechanism of QGYD in sensitizing LVFX against MDR PA infection.

MATERIALS AND METHODS

Pulmonary infections were induced in rats by MDR PA. The changes in pharmacokinetics-pharmacodynamics (PK-PD) parameters of LVFX after combined with QGYD were investigated in MDR PA-induced rats. Subsequently, the correlation between PK and PD was analyzed and PK-PD models were established to elucidate the relationship between QGYD-induced alterations in LVFX metabolism and its sensitization to LVFX. Antibody chip technology was used to detect the levels of inflammatory factors, suggesting the relationship between the beneficial effect of immune regulation and the sensitization of QGYD.

RESULTS

QGYD significantly enhanced the therapeutic efficacy of LVFX against MDR PA infection. The combination of QGYD changed the PK parameters of LVFX such as T, t, MRT, V/F, CL/F and PD parameters such as MIC, AUC/MIC. Predicted results from PK-PD models demonstrated that the antibacterial effect of LVFX was significantly enhanced with the combination of QGYD, consistent with experimental findings. Antibody chip results revealed that the combination of QGYD made IL-1 β, IL-6, TNF- α, IL-10, and MCP-1 levels more akin to those of the blank group.

CONCLUSION

These findings indicated that QGYD could change the PK-PD behaviors of LVFX and help the body restore immune balance faster. This implied that a potential drug interaction might occur between QGYD and LVFX, leading to improved clinical efficacy when combined.

摘要

背景

芪归银汤(QGYD)是一种中药,其与左氧氟沙星(LVFX)联合应用已被证实在耐多药铜绿假单胞菌(MDR PA)感染的临床治疗中有效。本研究探讨了芪归银汤在使LVFX对MDR PA感染敏感化方面的治疗效果及可能机制。

材料与方法

用MDR PA诱导大鼠发生肺部感染。在MDR PA诱导的大鼠中研究LVFX与芪归银汤联合后药代动力学-药效学(PK-PD)参数的变化。随后,分析PK与PD之间的相关性并建立PK-PD模型,以阐明芪归银汤引起的LVFX代谢改变与其对LVFX的敏感化之间的关系。采用抗体芯片技术检测炎症因子水平,提示免疫调节有益作用与芪归银汤敏感化之间的关系。

结果

芪归银汤显著增强了LVFX对MDR PA感染的治疗效果。芪归银汤的联合使用改变了LVFX的PK参数,如T、t、MRT、V/F、CL/F以及PD参数,如MIC、AUC/MIC。PK-PD模型的预测结果表明,芪归银汤联合使用显著增强了LVFX的抗菌效果,与实验结果一致。抗体芯片结果显示,芪归银汤联合使用使IL-1β、IL-6、TNF-α、IL-10和MCP-1水平更接近空白组。

结论

这些发现表明,芪归银汤可改变LVFX的PK-PD行为,并有助于机体更快恢复免疫平衡。这意味着芪归银汤与LVFX之间可能发生潜在的药物相互作用,联合使用时可提高临床疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b8e/11141581/5999e53e0752/IDR-17-2089-g0001.jpg

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