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重新利用辛伐他汀治疗感染:一项研究。

Repurposing simvastatin for treatment of infections: and study.

作者信息

Moglad Ehssan, Elekhnawy Engy, Alanazi Nuor, Al-Fakhrany Omnia Momtaz

机构信息

Department of Pharmaceutics, College of Pharmacy, Prince Sattam bin Abdulaziz University, Alkharj, Saudi Arabia.

Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

出版信息

Biofouling. 2024 Nov;40(10):801-815. doi: 10.1080/08927014.2024.2413652. Epub 2024 Oct 10.

DOI:10.1080/08927014.2024.2413652
PMID:39390775
Abstract

Simvastatin had minimum inhibitory concentrations of 32 to 128 µg/mL against Klebsiella pneumoniae isolates and hindered the biofilm-formation ability of 58.54% of the isolates. It considerably diminished the bacterial cell counts in the biofilms as revealed by scanning electron microscope. Also, qRT-PCR revealed a downregulation of the biofilm genes (bcsA, wza, and luxS) by simvastatin in 48.78% of the isolates. Moreover, simvastatin has significantly improved the survival of mice and decreased the burden of bacteria in the infected lungs. Also, the histological architecture was substantially improved in the simvastatin-treated group, as the alveolar sacs and bronchioles appeared normal with minimal collagen fiber deposition. The immunohistochemical studies exposed that the TNF-α, NF-kβ, and COX-2 immunostaining considerably declined in the simvastatin-treated group. Furthermore, ELISA exposed that both IL-1β and IL-6 were considerably diminished in the lungs of the simvastatin-treated group.

摘要

辛伐他汀对肺炎克雷伯菌分离株的最低抑菌浓度为32至128μg/mL,并抑制了58.54%的分离株形成生物膜的能力。扫描电子显微镜显示,它显著减少了生物膜中的细菌细胞数量。此外,qRT-PCR显示,48.78%的分离株中,辛伐他汀下调了生物膜基因(bcsA、wza和luxS)。此外,辛伐他汀显著提高了小鼠的存活率,并减轻了感染肺部的细菌负荷。而且,辛伐他汀治疗组的组织学结构有显著改善,肺泡囊和细支气管外观正常,胶原纤维沉积极少。免疫组织化学研究表明,辛伐他汀治疗组中TNF-α、NF-kβ和COX-2免疫染色显著下降。此外,ELISA显示,辛伐他汀治疗组肺部的IL-1β和IL-6均显著减少。

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