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银纳米粒子-多糖对博来霉素诱导的大鼠肺纤维化的影响。

Effects of silver nanoparticles-polysaccharide on bleomycin-induced pulmonary fibrosis in rats.

机构信息

Department of Radioisotopes, Nuclear Research Centre, Atomic Energy Authority, Egypt.

Department of Pathology, National Cancer Institute, Cairo University, Egypt.

出版信息

J Pharm Pharmacol. 2021 Oct 7;73(11):1503-1512. doi: 10.1093/jpp/rgab037.

DOI:10.1093/jpp/rgab037
PMID:34515769
Abstract

OBJECTIVES

The first goal of this study was to synthesize the silver nanoparticles Alcaligenes xylosoxidans exopolysaccharide (Ag-AXEPS). The second objective was to analyse the role of Ag-AXEPS nanoparticles (NPS) in treating bleomycin (BLM)-induced lung fibrosis.

METHODS

Intratracheal bleomycin (2.5 U/kg) was administered to prompt pulmonary fibrosis in rats, and pulmonary fibrosis was treated with Ag-AXEPS nanoparticles (100 ppm/twice a week for four weeks).

KEY FINDINGS

Ag-AXEPS nanoparticles significantly decreased the diversity of pulmonary inflammatory agents in rats with BLM-induced fibrosis. Reduced levels of respiratory tumor necrosis factor-alpha, monocyte chemotactic protein-1, matrix metalloproteinases (MMP-2 and MMP-9) were observed on treatment with synthesized Ag-AXEPS. Similarly, the treatment decreased IL-12, mRNA levels of BAX and plasma fibrosis markers like N-terminal procollagen III propeptide and transforming growth factor-β1. On the other hand, the treatment increased mRNA BCL2 and total antioxidant capacity. It also lowered the level of fibrosis, as was shown by a quantified pathologic study of hematoxylin-eosin-stained lung parts. The treatment, however, ensured that lung collagen was restored, as assessed by Masson's trichrome stain, and that overall survival was increased and enhanced.

CONCLUSIONS

Our work showed that nanoparticles could be obtained at 37°C and may be a possible pulmonary fibrosis therapeutic agent.

摘要

目的

本研究的首要目标是合成粘质沙雷氏菌胞外多糖(Ag-AXEPS)的银纳米颗粒。其次是分析 Ag-AXEPS 纳米颗粒(NPS)在治疗博来霉素(BLM)诱导的肺纤维化中的作用。

方法

通过气管内注射博来霉素(2.5 U/kg)来促使大鼠发生肺纤维化,并使用 Ag-AXEPS 纳米颗粒(100 ppm/每周两次,共四周)治疗肺纤维化。

主要发现

Ag-AXEPS 纳米颗粒可显著降低博来霉素诱导纤维化大鼠肺部炎症因子的多样性。合成的 Ag-AXEPS 治疗后,呼吸肿瘤坏死因子-α、单核细胞趋化蛋白-1、基质金属蛋白酶(MMP-2 和 MMP-9)的水平降低。同样,该治疗降低了白细胞介素-12、BAX 的 mRNA 水平以及血浆纤维化标志物如 N 端前胶原 III 前肽和转化生长因子-β1。另一方面,该治疗增加了 BCL2 的 mRNA 水平和总抗氧化能力。通过对苏木精-伊红染色的肺组织进行定量病理研究表明,该治疗降低了纤维化程度。Masson 三色染色评估表明,治疗后肺胶原得到恢复,总生存率提高。

结论

我们的工作表明,纳米颗粒可在 37°C 下获得,可能成为一种潜在的肺纤维化治疗药物。

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