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他汀类药物对多物种口腔生物膜的影响表明辛伐他汀是一种针对牙龈卟啉单胞菌的药物候选物。

Effects of statins on multispecies oral biofilm identify simvastatin as a drug candidate targeting Porphyromonas gingivalis.

机构信息

Department of Microbiology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Kraków, Poland.

Department of Clinical Science, Broegelmann Research Laboratory, University of Bergen, Bergen, Norway.

出版信息

J Periodontol. 2019 Jun;90(6):637-646. doi: 10.1002/JPER.18-0179. Epub 2018 Dec 26.

Abstract

BACKGROUND

Statins effectively reduce risk of cardiovascular-related morbidity and mortality in patients with hyperlipidemia, hypertension, or type 2 diabetes. In addition to lowering cholesterol levels, several studies have attributed statins with immunomodulatory and bactericidal properties. Therefore, the aim of this study was to investigate statins' antimicrobial activity against periodontal homeostasis bacteria.

METHODS

Statin effect on bacterial growth was tested using planktonic monocultures and multibacterial biofilms. The latter consisted of five microbial species (Porphyromonas gingivalis, Fusobacterium nucleatum, Actinomyces naeslundii, Tannerella forsythia, and Streptococcus gordonii) associated with dysbiosis of the oral microbiota underlying establishment and perpetuation of periodontitis.

RESULTS

All four tested statins efficiently inhibited P. gingivalis growth and significantly decreased the cumulative bacterial load in developing and established biofilms. Simvastatin was most efficient and decreased P. gingivalis counts more than 1,300-fold relative to the control.

CONCLUSIONS

These findings suggest that similar effects on bacterial composition of the dental plaque may occur in vivo in patients on statins, thus, leading to a shift of the oral microbiome from a dysbiotic to a more homeostatic one. Simvastatin, being highly effective against P. gingivalis while not affecting commensal microbiota, possesses many properties qualifying it as a potential adjunctive treatment for chronic periodontitis. Further studies are needed to evaluate whether similar effects on bacterial composition of the dental plaque may occur in vivo in patients on statins, thus, leading to a shift of the oral microflora from dysbiotic to a more homeostatic one.

摘要

背景

他汀类药物可有效降低高血脂、高血压或 2 型糖尿病患者发生心血管相关发病率和死亡率。除了降低胆固醇水平外,几项研究还将他汀类药物归因于具有免疫调节和杀菌特性。因此,本研究旨在研究他汀类药物对牙周稳态细菌的抗菌活性。

方法

使用浮游单培养物和多细菌生物膜来测试他汀类药物对细菌生长的影响。后者由五种微生物物种(牙龈卟啉单胞菌、核梭杆菌、奈瑟氏放线菌、福赛斯坦纳菌和戈登链球菌)组成,这些微生物与口腔微生物群落的失调有关,而口腔微生物群落的失调是牙周炎发生和持续的基础。

结果

四种测试的他汀类药物均能有效抑制牙龈卟啉单胞菌的生长,并显著降低发育中和已建立的生物膜中累积的细菌负荷。辛伐他汀的效果最为显著,与对照组相比,牙龈卟啉单胞菌的数量减少了 1300 多倍。

结论

这些发现表明,在接受他汀类药物治疗的患者中,类似的对牙菌斑细菌组成的影响可能在体内发生,从而导致口腔微生物群从失调状态转变为更稳态。辛伐他汀对牙龈卟啉单胞菌具有高度有效性,而不影响共生菌群,具有许多特性,使其有资格成为慢性牙周炎的潜在辅助治疗方法。需要进一步研究以评估在接受他汀类药物治疗的患者中,类似的对牙菌斑细菌组成的影响是否可能在体内发生,从而导致口腔微生物群从失调状态转变为更稳态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f67c/6545270/20f95c6cd868/nihms-998649-f0001.jpg

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本文引用的文献

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Periodontal Microbiology.牙周微生物学
Dent Clin North Am. 2017 Apr;61(2):253-269. doi: 10.1016/j.cden.2016.11.005.
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Novel applications of statins for bone regeneration.他汀类药物在骨再生中的新应用。
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