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短期口服介孔二氧化硅纳米颗粒可能通过改变肠道微生物群引起大鼠结肠炎症。

Short-Term Oral Administration of Mesoporous Silica Nanoparticles Potentially Induced Colon Inflammation in Rats Through Alteration of Gut Microbiota.

机构信息

State Key Laboratory of Quality Research in Chinese Medicine & School of Pharmacy, Macau University of Science and Technology, Taipa, Macau SAR, People's Republic of China.

Institute of Material Medica, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.

出版信息

Int J Nanomedicine. 2021 Feb 5;16:881-893. doi: 10.2147/IJN.S295575. eCollection 2021.

Abstract

PURPOSE

Mesoporous silica (MSNs) have attracted considerable attention for its application in the field of drug delivery and biomedicine due to its high surface area, large pore volume, and low toxicity. Recently, numerous studies revealed that gut microbiota is of critical relevance to host health. However, the toxicological studies of MSNs were mainly based on the degradation, biodistribution, and excretion in mammalian after oral administration for now. Here in this study, we explored the impacts of oral administration of three kinds of MSNs on gut microbiota in rats to assess its potential toxicity.

METHODS

Forty rats were divided into four groups: control group; Mobil Composition of Matter No. 41 type mesoporous silica (MCM-41) group; Santa Barbara Amorphous-15 type mesoporous silica (SBA-15) group, and biodegradable dendritic center-radial mesoporous silica nanoparticle (DMSN) group. Fecal samples were collected 3 days and 7 days after the intake of MSNs and analyzed with high throughput sequencing. Gastric tissues in rats were obtained after dissection for the histological study.

RESULTS

Three different MSNs (MCM-41, SBA-15, and DMSN) were successfully prepared in this study. The pore size of three MSNs was calculated similarly as (3.54 ± 0.15) nm, (3.48 ± 0.21) nm, and (3.45 ± 0.17) nm according to the BET & BJH model, respectively, while the particle size of MCM-41, SBA-15 and DMSN was around 209.2 nm, 1349.56 nm, and 244.4 nm, respectively. In the gene analysis of 16S rRNA, no significant changes in the diversity and richness were found between groups, while decreased and increased in MCM-41 treated groups. Meanwhile, no inflammatory and erosion symptoms were observed in the morphological analysis of the colons, except the MCM-41 treated group.

CONCLUSION

Three different MSNs, MCM-41, SBA-15, and DMSN were successfully prepared, and this study firstly suggested the impact of MSNs on the gut microbiota, and further revealing the potential pro-inflammatory effects of oral administration of MCM-41 was possibly through the changing of gut microbiota.

摘要

目的

介孔硅(MSNs)由于其高比表面积、大孔体积和低毒性,在药物输送和生物医学领域得到了广泛关注。最近,大量研究表明,肠道微生物群对宿主健康至关重要。然而,目前 MSNs 的毒理学研究主要基于口服后在哺乳动物体内的降解、生物分布和排泄。在这项研究中,我们探讨了口服三种 MSNs 对大鼠肠道微生物群的影响,以评估其潜在毒性。

方法

将 40 只大鼠分为四组:对照组; Mobil Composition of Matter No. 41 型介孔硅(MCM-41)组;圣巴巴拉无定形-15 型介孔硅(SBA-15)组和可生物降解的树突状中心-径向介孔硅纳米颗粒(DMSN)组。在摄入 MSNs 后 3 天和 7 天收集粪便样本,并进行高通量测序分析。解剖后获取大鼠胃组织进行组织学研究。

结果

本研究成功制备了三种不同的 MSNs(MCM-41、SBA-15 和 DMSN)。根据 BET&BJH 模型,三种 MSNs 的孔径分别计算为(3.54±0.15)nm、(3.48±0.21)nm 和(3.45±0.17)nm,而 MCM-41、SBA-15 和 DMSN 的粒径分别约为 209.2nm、1349.56nm 和 244.4nm。在 16S rRNA 基因分析中,各组间多样性和丰富度无显著变化,而 MCM-41 处理组 减少, 增加。同时,除 MCM-41 处理组外,结肠形态分析未见炎症和侵蚀症状。

结论

成功制备了三种不同的 MSNs,MCM-41、SBA-15 和 DMSN。本研究首次提出了 MSNs 对肠道微生物群的影响,并进一步揭示了口服 MCM-41 可能通过改变肠道微生物群产生潜在的促炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3467/7872941/df0bed80bbf8/IJN-16-881-g0001.jpg

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