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Preventive effects of the novel antimicrobial peptide Nal-P-113 in a rat Periodontitis model by limiting the growth of Porphyromonas gingivalis and modulating IL-1β and TNF-α production

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单位: [1]China Med Univ, Sch Stomatol, Dept Periodont & Oral Biol, Shenyang 110002, Liaoning, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Pharm, Wuhan 430030, Hubei, Peoples R China [3]Natl Tsing Hua Univ, Inst Biotechnol, Hsinchu 300, Taiwan [4]Natl Tsing Hua Univ, Dept Med Sci, Hsinchu 300, Taiwan [5]Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 USA
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关键词: Antimicrobial peptide Animal model Periodontitis Alveolar bone loss Inflammatory response Porphyromonas gingivalis

摘要:
Background: P-113 (AKRHHGYKRKFH- NH2) is a 12-amino-acid histidine-rich peptide derived from histatin 5 that is highly degradable in high salt concentrations and biological fluids such as serum, plasma and saliva. Nal-P-113, a novel antimicrobial peptide whose histidine residues are replaced by the bulky amino acids beta-naphthylalanine, causes the antimicrobial peptide to retain its bactericidal activity even in physiological environments. This study evaluated the effect of the novel antimicrobial peptide Nal-P-113 in a rat periodontitis model and the mechanisms of action of Nal-P-113 for suppressing periodontitis. Methods: Periodontitis was induced in mandibular first molars in rats receiving a ligature and infected with Porphyromonas gingivalis. Animals were randomly divided into six groups: a, P. gingivalis W83 alone; b, P. gingivalis W83 with 6.25 mu g/mL of Nal-P-113; c, P. gingivalis W83 with 25 mu g/mL of Nal-P-113; d, P. gingivalis W83 with 100 mu g/mL of Nal-P-113; e, P. gingivalis W83 with 400 mu g/mL of Nal-P-113; and f, control without P. gingivalis W83 or Nal-P-113. Morphometric analysis was used to evaluate alveolar bone loss. Microbiological assessment of the presence of Porphyromonas gingivalis and total bacteria was performed using absolute quantitative real-time PCR and scanning electron microscopy. Gingival tissue was collected for western blot and immunohistochemical assays of IL-1 beta and TNF-alpha levels. Results: Alveolar bone loss was inhibited by 100 mu g/mL or 400 mu g/mL of Nal-P-113 compared to the control group (P < 0.05). Lower amounts of P. gingivalis and total bacteria were found in groups d and e compared with group a (P < 0.05). A decrease in the levels of IL-1 beta and TNF-alpha was detected in group d and group e compared to the control group (P < 0.05). The amount of P. gingivalis was positively correlated with IL-1 beta and TNF-alpha expression in periodontal tissue (P < 0.05). Conclusions: Nal-P-113 exhibited protective effects on Porphyromonas gingivalis-induced periodontitis in rats by limiting the amount of bacteria and modulating IL-1 beta and TNF-alpha production. The use of Nal-P-113 in vivo might serve as a beneficial preventive or therapeutic approach for periodontitis.

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出版当年[2016]版:
大类 | 4 区 医学
小类 | 3 区 全科医学与补充医学
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Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE
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第一作者单位: [1]China Med Univ, Sch Stomatol, Dept Periodont & Oral Biol, Shenyang 110002, Liaoning, Peoples R China
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