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| The Impact of Nobiletin on the Inflammatory Injury in Rats with Periodontitis by Regulating the CCL2-CCR2 Signaling Axis |
| YU Jinxian, YU Mei, LI Na |
| Wuhan Hospital of Traditional Chinese Medicine, Hubei Wuhan 430000, China |
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Abstract Objective: To investigate the effects of Nobiletin on inflammatory injury in periodontal disease rats and its mechanism by constructing a model of periodontitis rats. Methods: The rat model of periodontal disease was established by silk thread ligation and 10% sucrose drinking water; periodontal disease rats were separated into a model group, a low-dose Nobiletin group, a medium dose Nobiletin group, and a high-dose Nobiletin group, with 10 rats in each group. Another 10 rats were selected as the control group. The low, medium and high dose Nobiletin groups were administrated with 25mg/kg, 50mg/kg and 100 mg/kg, respectively, while the control group and model group were orally administrated with the same amount of normal saline. HE staining was performed to detect pathological changes in the periodontal tissue of rats in each group; qPCR was applied to measure the levels of C-C chemokine ligand 2 (CCL2), C-C chemokine receptor 2 (CCR2), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 mRNA in periodontal tissues of rats in each group. Immunohistochemical staining was applied to detect the expression of CCL2 in the periodontal tissue of rats in each group; Western blot was applied to detect the expression of CCL2, CCR2, TNF-α, IL-1β, and IL-6 proteins in the periodontal tissue of rats in each group. Results: Four weeks after the establishment of the periodontal disease rat model, compared with the control group, the model rats showed alveolar bone resorption, tooth root loosening and bleeding, indicated that the establishment of the periodontal disease rat model was successful; compared with the control group, the periodontal tissue of rats in the model group showed alveolar bone resorption, with a large number of inflammatory cell infiltration, the number of CCL2 positive cells increased, the mRNA and protein levels of CCL2, CCR2, TNF-α, IL-1β, IL-6 in periodontal tissue were obviously increased (P<0.05); compared with the model group, the inflammatory cell infiltration in the periodontal tissue of rats in the low, middle and high dose Nobiletin groups gradually reduced, the number of fibroblasts gradually increased, the number of CCL2 positive cells decreased, the levels of CCL2, CCR2, TNF-α, IL-1β, and IL-6 in periodontal tissue were obviously reduced, were dose-dependent (P<0.05). Conclusion: Nobiletin may alleviate the inflammatory injury of periodontal disease rats by inhibiting the CCL2-CCR2 signal axis.
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2023, Vol. 29 
