【摘要】 该文主要探讨冬凌草甲素(Ori)调节细胞外信号调节激酶(ERK)/丝裂原活化蛋白激酶(MAPK)信号通路对正畸牙移动(OTM)模型大鼠牙周炎症及破骨细胞的影响。通过构建OTM大鼠模型,将建模成功的大鼠随机分为OTM组、Ori低剂量组(Ori-L组)、Ori高剂量组(Ori-H组)、阳性药物甲硝唑(MTZ)组(MTZ组)、Ori高剂量+ERK/MAPK信号通路激活剂Anisomycin组(OriH+Anisomycin组),另外随机选取等数量的正常大鼠为Con组(对照组)。测量各组大鼠OTM距离;检测各组大鼠血清炎症相关因子水平;检测各组大鼠牙周组织病理变化及破骨细胞活性;检测各组大鼠牙周组织骨保护素(OPG)、核因子κB受体活化因子配体(RANKL)、骨形态发生蛋白-2(BMP-2)以及ERK/MAPK信号通路相关蛋白表达情况。结果显示:与Con组比较, OTM组大鼠压力侧牙周组织纤维排列紊乱,大量多核破骨细胞聚集于吸收陷窝, OTM距离,血清IL-6、IFN-γ、PGE2水平,破骨细胞数量,以及RANKL、BMP-2、p-ERK1/2/ERK1/2、p-p38 MAPK/p38 MAPK水平升高, OPG表达水平降低(P<0.05);与OTM组比较, Ori-L组、Ori-H组、MTZ组大鼠压力侧牙周组织纤维排列恢复,多核破骨细胞数量减少,病理损伤恢复,血清IL-6、IFN-γ、PGE2水平,破骨细胞数量以及RANKL、p-ERK1/2/ERK1/2、p-p38 MAPK/p38 MAPK水平降低, OTM距离以及BMP-2、OPG表达水平升高(P<0.05);与Ori-H组比较, Ori-H+Anisomycin组大鼠压力侧牙周组织病理损伤加重,纤维排列紊乱,血清IL-6、IFN-γ、PGE2水平,破骨细胞数量,以及RANKL、p-ERK1/2/ERK1/2、p-p38MAPK/p38 MAPK水平升高, OTM距离以及BMP-2、OPG表达水平降低(P<0.05)。综上,该研究表明Ori能够抑制OTM大鼠牙周炎症和破骨细胞活化,进而促进OTM,可能与抑制ERK/MAPK信号通路密切相关。更多还原

【Abstract】 This article mainly investigates the effects of Ori(oridonin) on periodontal inflammation and osteoclasts in OTM(orthodontic tooth movement) model rats by regulating the ERK/MAPK(extracellular regulated protein kinase/mitogen-activated protein kinase) signaling pathway. After successfully establishing the OTM rat model, the modeled rats were randomly divided into five groups: OTM group, Ori-L group(Ori low-dose group), Ori-H group(Ori high-dose group), positive drug MTZ(metronidazole) group(MTZ group), and Ori high-dose+ERK/MAPK signaling pathway activator Anisomycin group(Ori-H+Anisomycin group). In addition, an equal number of normal rats were randomly selected as the Con group(Control group). The OTM distance in each group of rats was measured. The levels of serum inflammation related factors were detected. The pathological changes and osteoclast activity of periodontal tissues were assessed. The expression levels of OPG(osteoprotegerin), RANKL(receptor activator of nuclear factor kappa B ligand), BMP-2(bone morphogenetic protein-2), and ERK/MAPK signaling pathway-related proteins in periodontal tissues were determined. Compared with the Con group, rats in the OTM group exhibited disordered arrangement of periodontal tissue fibers on the pressure side, with a large number of multinucleated osteoclasts accumulating in bone resorption lacunae; the OTM distance, serum levels of IL-6, IFN-γ and PGE2, osteoclast count, as well as the levels of RANKL, BMP-2, p-ERK1/2/ERK1/2, and p-p38 MAPK/p38 MAPK were significantly increased, while the expression level of OPG was significantly decreased(P<0.05). Compared with rats in the OTM group, rats in the Ori-L group, Ori-H group, and MTZ group showed restored arrangement of periodontal tissue fibers on the pressure side, reduced number of multinucleated osteoclasts, and alleviated pathological damage; the serum levels of IL-6, IFN-γ, PGE2, osteoclast count, as well as the levels of RANKL, pERK1/2/ERK1/2, p-p38 MAPK/p38 MAPK were significantly decreased, while the OTM distance and the expression levels of BMP-2, and OPG were significantly increased(P<0.05). Compared with rats in the Ori-H group, rats in the Ori-H+Anisomycin group showed aggravated pathological damage and disordered fiber arrangement of periodontal tissue fibers on the pressure side; the serum levels of IL-6, IFN-γ, PGE2, osteoclast count, as well as the levels of RANKL, p-ERK1/2/ERK1/2, p-p38 MAPK/p38 MAPK were significantly increased, while the OTM distance, the expression levels of BMP-2 and OPG were decreased(P<0.05). In conclusion, this study demonstrates that Ori can inhibit periodontal inflammation and osteoclast activation in OTM rats, thereby promoting OTM, which may be closely related to the inhibition of the ERK/MAPK signaling pathway.更多还原