Department of Pediatric and Preventive Dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China.
Department of Pediatric and Preventive Dentistry, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing 210029, China.
Int Immunopharmacol. 2021 Jun;95:107505. doi: 10.1016/j.intimp.2021.107505. Epub 2021 Mar 13.
The purpose of the present study was to investigate the pharmacological effect of Fisetin on experimental periodontitis in rats and explore its potential mechanism. The ligature/LPS method was used to induce periodontitis in rats. LPS was employed to cause inflammation in Human gingival fibroblasts (HGF). The transfections with FGFR1 SiRNA, NLRP3 SiRNA and the selective TLR4 inhibitor TAK242 were used to investigate the mechanism of Fisetin-mediated inflammatory reaction in LPS-induced HGF. As a result, Fisetin reduced the alveolar bone gap, reversed histopathological lesion and inhibited serum inflammatory cytokine concentration in periodontitis rats. Fisetin decreased the inflammatory cytokine contents in the supernatant of LPS-induced HGF. The inhibitory effect of Fisetin might be attributed to FGFR1/TLR4/NLRP3 inflammasome pathway both in vivo and in vitro. The suppressions of FGFR1, TLR4 and NLRP3 proved that FGFR1/TLR4/NLRP3 signaling was involved in the Fisetin-mediated inflammatory response. Fisetin also inhibited NLRP3 priming. The data demonstrated that Fisetin attenuated periodontitis by inhibiting inflammatory reaction via FGFR1/TLR4/NLRP3 inflammasome pathway.
本研究旨在探讨非瑟酮对大鼠实验性牙周炎的药理作用，并探讨其潜在机制。采用结扎/LPS 法诱导大鼠牙周炎，LPS 诱导人牙龈成纤维细胞（HGF）产生炎症。用 FGFR1 SiRNA、NLRP3 SiRNA 和选择性 TLR4 抑制剂 TAK242 转染来探讨非瑟酮介导的 LPS 诱导的 HGF 炎症反应的机制。结果表明，非瑟酮减少了牙槽骨间隙，逆转了组织病理学损伤，并抑制了牙周炎大鼠血清中炎症细胞因子的浓度。非瑟酮降低了 LPS 诱导的 HGF 上清液中炎症细胞因子的含量。体内外研究均表明，非瑟酮的抑制作用可能归因于 FGFR1/TLR4/NLRP3 炎性小体通路。抑制 FGFR1、TLR4 和 NLRP3 证实了 FGFR1/TLR4/NLRP3 信号通路参与了非瑟酮介导的炎症反应。非瑟酮还抑制了 NLRP3 的引发。数据表明，非瑟酮通过抑制 FGFR1/TLR4/NLRP3 炎性小体通路抑制炎症反应从而减轻牙周炎。
