[1]纪亚楠,李旭华,冯云,等.橙皮苷对牙髓炎大鼠牙髓组织损伤的作用及机制实验研究[J].陕西医学杂志,2025,54(8):1017-1022.[doi:DOI:10.3969/j.issn.1000-7377.2025.08.002]
　JI Yanan,LI Xuhua,FENG Yun,et al.Effect and mechanism of hesperidin on pulp tissue damage in rats with pulpitis[J].,2025,54(8):1017-1022.[doi:DOI:10.3969/j.issn.1000-7377.2025.08.002]
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橙皮苷对牙髓炎大鼠牙髓组织损伤的作用及机制实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
54
期数:
2025年8期
页码:
1017-1022
栏目:
基础研究
出版日期:
2025-08-05

文章信息/Info

Title:
Effect and mechanism of hesperidin on pulp tissue damage in rats with pulpitis
作者:
纪亚楠1; 李旭华1; 冯云1; 储雯2; 李鹏1
（1.云南省第三人民医院口腔科，云南 昆明 650216；2.云南大学附属医院口腔预防科，云南 昆明 650011）
Author(s):
JI Yanan1; LI Xuhua1; FENG Yun1; CHU Wen2; LI Peng1
(1.Department of Stomatology,the Third People’s Hospital of Yunnan Province,Kunming 650216,China;2.Department of Oral Prevention,Affiliated Hospital of Yunnan University,Kunming 650011,China)
关键词:
牙髓炎; 橙皮苷; 细胞外信号调节激酶1/2-丝裂原活化蛋白激酶信号通路; 巨噬细胞极化; 炎症反应; 大鼠
Keywords:
Pulpitis; Hesperidin; ERK1/2-MAPK signaling pathway; Macrophage polarization; Inflammatory response; Rats
分类号:
R -33
DOI:
DOI:10.3969/j.issn.1000-7377.2025.08.002
文献标志码:
A
摘要:
目的：探讨橙皮苷对牙髓炎大鼠牙髓组织损伤的作用，并基于细胞外信号调节激酶1/2-丝裂原活化蛋白激酶（ERK1/2-MAPK）信号通路分析其潜在作用机制。方法：采用脂多糖（LPS）构建牙髓炎大鼠模型。将造模成功的大鼠随机分为模型组、橙皮苷低剂量组和橙皮苷高剂量组，每组15只。另随机选取15只正常大鼠为对照组。橙皮苷低、高剂量组大鼠分别腹腔注射5、20 mg/kg橙皮苷溶液，1次/d，连续5 d；对照组和模型组大鼠同时腹腔注射等体积0.9%氯化钠溶液。干预结束后，观察各组大鼠一般行为学变化；HE染色观察大鼠牙髓组织病理学变化；ELISA法检测大鼠血清肿瘤坏死因子-α（TNF-α）、白细胞介素-4（IL-4）、IL-6水平；采用实时荧光定量聚合酶链反应（RT-qPCR）检测大鼠牙髓组织中M1型巨噬细胞极化标志物[诱导型一氧化氮合酶（iNOS）、白细胞分化抗原68（CD68）]和M2型巨噬细胞极化标志物[精氨酸酶-1（Arg-1）、CD206]mRNA表达；Western blot检测大鼠牙髓组织磷酸化ERK1/2（p-ERK1/2）、ERK1/2、磷酸化p38蛋白激酶（p-p38）、p38蛋白表达水平。结果：与对照组比较，模型组大鼠采食量减少，精神状态不佳，成牙本质细胞排列紊乱，牙髓组织充血扩张，炎症细胞浸润增加，血清TNF-α、IL-6水平、牙髓组织CD68、iNOS mRNA以及p-ERK1/2、p-p38蛋白表达水平升高，血清IL-4水平、牙髓组织CD206、Arg-1 mRNA表达水平降低（均P＜0.05）。与模型组比较，橙皮苷低、高剂量组大鼠采食和精神状态较好，成牙本质细胞排列紊乱情况、牙髓组织充血扩张情况以及炎症细胞浸润程度均有所减轻，血清TNF-α、IL-6水平、牙髓组织CD68、iNOS mRNA以及p-ERK1/2、p-p38蛋白表达水平降低，血清IL-4水平、牙髓组织CD206、Arg-1 mRNA表达水平升高（均P＜0.05）。橙皮苷高剂量组上述指标优于橙皮苷低剂量组（均P＜0.05）。结论：橙皮苷能够抑制M1型巨噬细胞极化，促进M2型巨噬细胞极化，减轻炎症反应，改善牙髓炎大鼠牙髓组织损伤，其作用机制可能与抑制ERK1/2-MAPK信号通路激活有关。
Abstract:
Objective:To investigate the effect of hesperidin on pulp tissue damage in rats with pulpitis and analyze its potential mechanisms based on the extracellular signal-regulated kinase 1/2 (ERK1/2)-mitogen-activated protein kinase (MAPK) signaling pathway.Methods：The rat model of pulpitis was established by LPS.The successfully modeled rats were randomly divided into the model group,low-dose hesperidin group and high-dose hesperidin group,with 15 rats in each group.Another 15 normal rats were randomly selected as the control group.Rats in the low-dose and high-dose hesperidin groups were intraperitoneally injected with 5 and 20 mg/kg of hesperidin solution,respectively,once a day for 5 consecutive days.Rats in the control and model groups were simultaneously intraperitoneally injected with an equal volume of 0.9% sodium chloride solution.After the intervention,the general behavioral changes of the rats in each group were observed.The pathological changes in the pulp tissue of the rats were observed by HE staining.The levels of tumor necrosis factor-α (TNF-α),interleukin-4 (IL-4) and IL-6 in the rat serum were detected by ELISA.The mRNA expression of M1 macrophage polarization markers (iNOS,CD68) and M2 macrophage polarization markers (Arg-1,CD206) in rat pulp tissue was detected by RT-qPCR.The expression levels of phosphorylated ERK1/2 (p-ERK1/2),ERK1/2,phosphorylated p38 protein kinase (p-p38),and p38 protein in rat pulp tissue were detected by Western blot.Results:Compared with the control group,the rats in the model group exhibited decreased food intake,poor mental state,disordered arrangement of odontoblasts,pulp tissue congestion and dilation,increased infiltration of inflammatory cells,elevated levels of serum TNF-α and IL-6,increased mRNA expression of CD68 and iNOS in pulp tissue,and elevated protein expression levels of p-ERK1/2 and p-p38 in pulp tissue,while the levels of serum IL-4,mRNA expression of CD206 and Arg-1 in pulp tissue were decreased (all P<0.05).Compared with the model group,the rats in the low-dose and high-dose hesperidin groups showed better food intake and mental state,improved arrangement of odontoblasts,reduced pulp tissue congestion and dilation,and decreased infiltration of inflammatory cells.The levels of serum TNF-α and IL-6,mRNA expression of CD68 and iNOS in pulp tissue,and protein expression levels of p-ERK1/2 and p-p38 in pulp tissue were decreased,while the levels of serum IL-4 and mRNA expression of CD206 and Arg-1 in pulp tissue were increased (all P<0.05).The high-dose hesperidin group showed better outcomes in these indicators compared with the low-dose hesperidin group (all P<0.05).Conclusion:Hesperidin can inhibit M1 macrophage polarization,promote M2 macrophage polarization,reduce inflammatory reactions,and improve pulp tissue damage in rats with pulpitis.Its mechanism of action may be related to the inhibition of the activation of the ERK1/2-MAPK signaling pathway.

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备注/Memo

备注/Memo:
云南省科技厅科技计划项目（202401AY070001-287）
更新日期/Last Update: 2025-08-04