Dionísio Thiago J, Souza Gabriela P, Colombini-Ishikiriama Bella L, Garbieri Thais F, Parisi Viviane A, Oliveira Gabriela M, Cano Isadora P, Rodini Camila O, Oliveira Sandra H P, Greene Andrew S, Santos Carlos F
Department of Biological Sciences, Bauru School of Dentistry, University of São Paulo, Bauru, São Paulo, Brazil.
Department of Basic Sciences, School of Dentistry, São Paulo State University-UNESP, Araçatuba, São Paulo, Brazil.
J Periodontol. 2020 Apr;91(4):533-544. doi: 10.1002/JPER.19-0064. Epub 2019 Sep 23.
The initiation and progression of periodontitis might involve a local renin-angiotensin system in periodontal tissue. This study hypothesized that Losartan treatment could promote protection to rats submitted to experimental periodontitis (EP) by attenuating alveolar bone loss due to reduction in inflammatory cytokines, better reactive oxidant species regulation and maintenance of the balance between bone formation and resorption factors.
One hundred and thirty rats were submitted to EP with a silk suture thread (4.0) placed around the lower right first molar for 1, 3, 7, and 14 consecutive days. The study comprised four groups: G1-control without EP; G2-animals with EP treated with water; G3-Losartan-treated animals (treatment started at the same day of EP induction), and G4-animals previously treated with Losartan for 30 days followed by induction of EP and continuity of treatment.
G2 rats had greater bone loss volume, increased number, and thickness and decreased separation of trabeculae. On the other hand, G4 animals showed significant improvements in these parameters. Histological analysis revealed that EP favors inflammatory cell infiltration and junctional epithelium, cementum with alveolar bone crest destruction, but animals pretreated with Losartan (G4) did not show these features. Although the G3 animals did not demonstrate the improvements detected in G4, mRNA expression results were similar. In mandibular tissue, EP promoted mRNA increases for ACE, AT1 receptor, and inflammatory mediators as well as decreases for antioxidant enzymes. However, Losartan treatments attenuated these responses in addition to promoting an increase in bone formation markers and transcription factors.
AT1 receptor modulates EP progression.
牙周炎的发生和发展可能涉及牙周组织中的局部肾素-血管紧张素系统。本研究假设,氯沙坦治疗可通过减少炎症细胞因子减轻牙槽骨吸收、更好地调节活性氧物种以及维持骨形成和吸收因子之间的平衡,从而促进对实验性牙周炎(EP)大鼠的保护。
130只大鼠通过在右下第一磨牙周围放置丝线(4.0)连续1、3、7和14天建立EP模型。该研究包括四组:G1-未患EP的对照组;G2-患EP并用水治疗的动物;G3-氯沙坦治疗的动物(在EP诱导当天开始治疗),以及G4-预先用氯沙坦治疗30天,随后诱导EP并继续治疗的动物。
G2组大鼠的骨吸收体积更大,小梁数量增加、厚度减小且间距减小。另一方面,G4组动物在这些参数上有显著改善。组织学分析显示,EP有利于炎症细胞浸润和结合上皮、牙骨质与牙槽嵴顶破坏,但预先用氯沙坦治疗的动物(G4)未表现出这些特征。尽管G3组动物未表现出G4组检测到的改善,但mRNA表达结果相似。在下颌组织中,EP促进了ACE、AT1受体和炎症介质的mRNA增加,以及抗氧化酶mRNA的减少。然而,氯沙坦治疗除了促进骨形成标志物和转录因子增加外,还减弱了这些反应。
AT1受体调节EP的进展。