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纳米胶束增强木犀草素在细菌诱导的肺部感染中的抗炎作用。

Improving Anti-Inflammatory Effect of Luteolin with Nano-Micelles in the Bacteria-Induced Lung Infection.

机构信息

Department of Pathophysiology, West China College of Basic and Forensic Medicine, Sichuan University, Chengdu, 610041, PR China.

Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, PR China.

出版信息

J Biomed Nanotechnol. 2021 Jun 1;17(6):1229-1241. doi: 10.1166/jbn.2021.3101.

Abstract

The effective therapy for lung infectious diseases became more and more difficult since the severe antibiotic resistance of pathogenic microorganisms, it is urgent to develop new antimicrobial agents. Luteolin has been reported to play a crucial part in host immune responses. However, the clinical use of luteolin is impeded due to its hydrophobicity and low oral bioavailability. In this study, we formulated luteolin-loaded Methoxy poly(ethylene glycol)-poly(lactide) micelles (luteolin/MPEG-PLA), to improve the bioavailability of luteolin in lung infectious diseases. The results showed that luteolin/MPEG-PLA treatment could reduce the adhesion of ) to lung epithelial cells and enhance the germicidal ability of macrophages against compared to untreated group. Meanwhile, luteolin/MPEG-PLA showed stronger adhesion resistance of epithelial cells and germicidal ability of macrophages compared with free luteolin. study, luteolin/MPEG-PLA administration significantly promoted the clearance of bacteria and reduced inflammatory infiltration of lung tissue in induced lung infectious mice model. Further studies showed that treatment with luteolin/MPEG-PLA reduced the mRNA expression of LPS-induced inflammatory cytokines and chemokines in macrophages significantly. In general, luteolin/MPEG-PLA can enhance the anti-bacterial ability of lung epithelial cells and macrophages, and has a stronger therapeutic effect than free luteolin in bacterial-induced lung infection. Luteolin/MPEG-PLA may be an excellent potential drug for bacterial-induced lung infectious diseases treatment.

摘要

由于致病微生物的严重抗生素耐药性,肺部感染性疾病的有效治疗变得越来越困难,因此迫切需要开发新的抗菌药物。木犀草素已被报道在宿主免疫反应中发挥关键作用。然而,由于其疏水性和低口服生物利用度,木犀草素的临床应用受到阻碍。在本研究中,我们制备了负载木犀草素的甲氧基聚乙二醇-聚乳酸(MPEG-PLA)胶束(木犀草素/MPEG-PLA),以提高肺部感染性疾病中木犀草素的生物利用度。结果表明,与未处理组相比,木犀草素/MPEG-PLA 处理可减少对肺上皮细胞的粘附,并增强巨噬细胞对的杀菌能力。同时,与游离木犀草素相比,木犀草素/MPEG-PLA 对上皮细胞的粘附抵抗力更强,对巨噬细胞的杀菌能力更强。在本研究中,木犀草素/MPEG-PLA 给药显著促进了细菌的清除,并减少了诱导的肺部感染小鼠模型中肺组织的炎症浸润。进一步的研究表明,木犀草素/MPEG-PLA 处理可显著降低 LPS 诱导的巨噬细胞中炎症细胞因子和趋化因子的 mRNA 表达。总之,木犀草素/MPEG-PLA 可以增强肺上皮细胞和巨噬细胞的抗菌能力,并且在细菌诱导的肺部感染中比游离木犀草素具有更强的治疗效果。木犀草素/MPEG-PLA 可能是治疗细菌诱导的肺部感染性疾病的一种极好的潜在药物。

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