木犀草素对牙周炎大鼠NLRP3/IL-1β信号通路及骨改建的影响

doi:10.13701/j.cnki.kqyxyj.2020.12.009

摘要/Abstract

摘要： 目的:探讨木犀草素对牙周炎大鼠核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)/白介素-1β(IL-1β)信号通路及骨改建的影响。方法:将SD雄性大鼠随机分为4组:对照组(灌胃等量生理盐水)、模型组(灌胃等量生理盐水)、木犀草素低、高剂量组(灌胃给予50 mg/kg、100 mg/kg木犀草素),每天1次,每组各10只,除对照组外,其它组大鼠制备牙周炎大鼠模型。连续给药7 d后,通过Micro-CT观察各组大鼠牙槽骨骨小梁数目(Tb.N)、骨小梁分离度(Tb.Sp)、骨小梁厚度(Tb.Th)及牙槽骨吸收情况;HE染色观察各组大鼠牙周组织病理变化;抗酒石酸酸性磷酸酶(TRAP)染色观察各组大鼠牙周组织破骨细胞数;免疫组织化学测定核因子κB受体活化因子配体(RANKL)和骨保护素(OPG)表达;蛋白免疫印迹(Western blot)法检测牙周组织中NLRP3、IL-1β蛋白表达。结果:与对照组相比,模型组大鼠牙周纤维排列紊乱,牙周膜狭窄,牙槽骨表面不平整有较多骨吸收陷窝,牙槽骨Tb.N、Tb.Th、牙周组织OPG表达显著降低(P＜0.05),Tb.Sp、CEJ-ABC值、牙周组织破骨细胞数、RANKL表达、NLRP3、IL-1β蛋白表达显著升高(P＜0.05);与模型组相比,木犀草素低、高剂量组大鼠牙周纤维排列较整齐,上述病理症状明显减轻,牙槽骨Tb.N、Tb.Th、牙周组织OPG表达依次升高(P＜0.05),Tb.Sp、CEJ-ABC值、牙周组织破骨细胞数、RANKL表达、NLRP3、IL-1β蛋白表达依次降低(P＜0.05)。结论:木犀草素可能通过抑制NLRP3/IL-1β信号通路,减轻牙周组织损伤、促进牙槽骨改建。

关键词: 木犀草素, 牙周炎, 核苷酸结合寡聚化结构域样受体蛋白3/白介素-1β信号通路, 骨改建

Abstract: Objective: To investigate the effects of luteolin on the signal pathway of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/interleukin-1β (IL-1β) and bone remodeling in periodontitis rats. Methods: SD male rats were randomly divided into four groups: control group (gavage with the same amount of saline), model group (gavage with the same amount of saline), luteolin low and high dose groups (given 50 mg/kg and 100 mg/kg luteolin by gavage), once a day, with 10 in each group. Except the control group, the other groups of rats were prepared with periodontitis model. After 7 days of continuous administration, the trabecular number (TB.N), trabecular separation (Tb.Sp), trabecular thickness (Tb.Th), and alveolar bone absorption were observed by Micro-CT. HE staining was used to observe the pathological changes of periodontal tissues. The number of osteoclasts in periodontal tissue was observed by tartrate resistant acid phosphatase (TRAP) staining. The expressions of nuclear factor κB receptor activator ligand (RANKL) and osteoprotegerin (OPG) were determined by immunohistochemistry. Western blot was used to detect the protein expressions of NLRP3 and IL-1β in periodontal tissues. Results: Compared with those in the control group, the periodontal fibers in the model group were disorganized, the periodontal membrane was narrow, the surface of alveolar bone was not smooth, and there were more bone resorption lacunae. TB.N and Tb.Th in alveolar bone and the expression of OPG in periodontal tissue were significantly lower (P<0.05), while Tb.Sp, CEJ-ABC value, osteoclast number, RANKL expression, NLRP3, and IL-1β protein expressions in periodontal tissue were significantly higher (P<0.05). Compared with those in the model group, the periodontal fibers in the low and high dose luteolin groups were arranged in order, and the above pathological symptoms were alleviated obviously, TB.N and Tb.Th in alveolar bone and the expression of OPG in periodontal tissue increased in turn (P<0.05), while Tb.Sp, CEJ-ABC value, osteoclast number, RANKL expression, NLRP3, and IL-1β protein expressions in periodontal tissue decreased in turn (P<0.05). Conclusion: Luteolin may reduce the periodontal tissue damage and promote the alveolar bone remodeling by inhibiting NLRP3/IL-1β signal pathway.

Key words: luteolin, periodontitis, nucleotide-binding oligomerization domain-like receptor protein 3/interleukin-1β signaling pathway, bone remodeling

李苑荟, 邢孔才, 王怡婷, 李小红. 木犀草素对牙周炎大鼠NLRP3/IL-1β信号通路及骨改建的影响[J]. 口腔医学研究, 2020, 36(12): 1117-1122.

LI Yuanhui, XING Kongcai, WANG Yiting , LI Xiaohong. Effects of Luteolin on NLRP3/IL-1β Signal Pathway and Bone Remodeling in Periodontitis Rats.[J]. Journal of Oral Science Research, 2020, 36(12): 1117-1122.

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