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牙龈卟啉单胞菌可诱导小鼠心肌炎和/或心肌梗死,IL-17A 参与这些疾病的发病机制。

Porphyromonas gingivalis induces myocarditis and/or myocardial infarction in mice and IL-17A is involved in pathogenesis of these diseases.

机构信息

Department of Microbiology, Kyoto Prefectural University of Medicine Graduate School of Medical Science, 465, Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

出版信息

Arch Oral Biol. 2011 Nov;56(11):1290-8. doi: 10.1016/j.archoralbio.2011.05.012. Epub 2011 Jun 16.

Abstract

OBJECTIVES

Although an association between periodontitis and cardiovascular diseases has been suggested, the role of Porphyromonas gingivalis in cardiovascular diseases is not clear. In this study, we examined whether experimental bacteremia of P. gingivalis causes cardiovascular diseases and investigated the mechanism of pathogenesis of cardiovascular diseases induced by P. gingivalis.

DESIGN

C57BL/6 mice were intravenously inoculated with 2.0 × 10(8)CFU of P. gingivalis A7436 strain. Mice were sacrificed at specified days and their hearts were collected. The collected organs were divided into two halves and used for histological evaluation and cytokine analysis. IL-17A(-/-), IFN-γ(-/-) and TNF-α(-/-) mice were also intravenously inoculated and the histological changes of hearts in mice were examined.

RESULTS

Myocarditis and/or myocardial infarction were observed in mice injected with P. gingivalis. The levels of IL1-β, IL-6, IL-17A, IL-18, TNF-α and IFN-γ mRNA increased significantly after P. gingivalis injection. In particular, high levels of IL-17A and IFN-γ mRNA expression were observed in hearts of mice after P. gingivalis injection in comparison with these levels before injection. Furthermore, the production of IL-17A was detected in hearts of wild-type mice after P. gingivalis injection. In wild-type, TNF-α(-/-) and IFN-γ(-/-) mice, moderate infiltration of neutrophils and monocytes was observed in hearts at 5 days after injection. In contrast, no inflammatory findings were observed in hearts of IL-17A(-/-) mice.

CONCLUSION

We have demonstrated that an experimental bacteremia of P. gingivalis could induce myocarditis and/or myocardial infarction in mice, and IL-17A plays an important role in the pathogenesis of these diseases.

摘要

目的

尽管牙周炎与心血管疾病之间存在关联,但牙龈卟啉单胞菌(Porphyromonas gingivalis)在心血管疾病中的作用尚不清楚。本研究旨在探讨实验性牙龈卟啉单胞菌菌血症是否会导致心血管疾病,并研究牙龈卟啉单胞菌诱导心血管疾病的发病机制。

设计

将 2.0×10(8)CFU 的牙龈卟啉单胞菌 A7436 株经静脉接种于 C57BL/6 小鼠。在特定天数处死小鼠,采集心脏。采集的器官分为两部分,用于组织学评估和细胞因子分析。此外,还对 IL-17A(-/-)、IFN-γ(-/-)和 TNF-α(-/-) 小鼠进行静脉接种,并检查小鼠心脏的组织学变化。

结果

牙龈卟啉单胞菌注射小鼠出现心肌炎和/或心肌梗死。牙龈卟啉单胞菌注射后,IL1-β、IL-6、IL-17A、IL-18、TNF-α 和 IFN-γ mRNA 水平显著升高。特别是,与注射前相比,牙龈卟啉单胞菌注射后小鼠心脏中 IL-17A 和 IFN-γ mRNA 的表达水平显著升高。此外,在牙龈卟啉单胞菌注射后的野生型小鼠心脏中检测到 IL-17A 的产生。在野生型、TNF-α(-/-)和 IFN-γ(-/-)小鼠中,注射后 5 天心脏中可见中性粒细胞和单核细胞中度浸润。相比之下,IL-17A(-/-)小鼠的心脏未观察到炎症表现。

结论

本研究表明,实验性牙龈卟啉单胞菌菌血症可诱导小鼠心肌炎和/或心肌梗死,IL-17A 在这些疾病的发病机制中发挥重要作用。

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