Prestifilippo J P, Fernández-Solari J, Martinel Lamas D J, Rios C E, Mohn C, Perazzo J C, Rivera E S, Elverdin J C, Medina V A
Physiology Department, School of Dentistry, University of Buenos Aires, Buenos Aires, Argentina.
National Scientific and Technical Research Council (CONICET), Buenos Aires, Argentina.
Oral Dis. 2016 Jul;22(5):423-9. doi: 10.1111/odi.12467. Epub 2016 Mar 28.
The objective of this study was to investigate whether histamine H4 receptor (H4 R) antagonists could prevent experimental periodontitis (EP)-induced histological, functional and inflammatory alterations in submandibular gland (SMG), periodontal bone and gingiva.
Bilateral EP was induced for 2 weeks in anaesthetized male rats. The effect of systemic and local administration of H4 R antagonists (JNJ7777120, JNJ10191584) on histopathology and functionality of SMG, bone loss and gingival inflammation was evaluated.
The subcutaneous administration of JNJ7777120 prevented periodontitis-induced SMG histological injury, reducing vacuolization and apoptosis and additionally reversed the increased prostaglandin E2 (PGE2) levels in SMG while it partially reversed the methacholine-induced salivation reduction produced by periodontitis. JNJ7777120 attenuated bone loss and the increased PGE2 levels and inflammatory infiltration in gingival tissue of rats with periodontitis. Finally, local administration of JNJ7777120 and JNJ10191584 was also beneficial for improving periodontal parameters.
H4 receptor antagonists are able to ameliorate periodontitis-induced injury on SMG, gingival tissue and bone structure, suggesting that pharmacological targeting of H4 R could be an attractive strategy to improve periodontal health.
本研究旨在调查组胺H4受体（H4R）拮抗剂是否能够预防实验性牙周炎（EP）引起的下颌下腺（SMG）、牙周骨和牙龈的组织学、功能及炎症改变。
在麻醉的雄性大鼠中诱导双侧EP持续2周。评估全身和局部给予H4R拮抗剂（JNJ7777120、JNJ10191584）对SMG的组织病理学和功能、骨质流失及牙龈炎症的影响。
皮下注射JNJ7777120可预防牙周炎诱导的SMG组织学损伤，减少空泡化和细胞凋亡，此外还可逆转SMG中前列腺素E2（PGE2）水平的升高，同时部分逆转牙周炎引起的乙酰甲胆碱诱导的唾液分泌减少。JNJ7777120减轻了牙周炎大鼠牙龈组织中的骨质流失、PGE2水平升高及炎症浸润。最后，局部给予JNJ7777120和JNJ10191584对改善牙周参数也有益处。
H4受体拮抗剂能够改善牙周炎对SMG、牙龈组织和骨结构造成的损伤，表明对H4R进行药物靶向治疗可能是改善牙周健康的一种有吸引力的策略。
