雷公藤甲素调控p38 MAPK/ERK/JNK信号通路对正畸牙移动模型大鼠牙周炎症及破骨细胞的影响

doi:10.13701/j.cnki.kqyxyj.2024.11.007

口腔医学研究 ›› 2024, Vol. 40 ›› Issue (11): 978-984.DOI: 10.13701/j.cnki.kqyxyj.2024.11.007

雷公藤甲素调控p38 MAPK/ERK/JNK信号通路对正畸牙移动模型大鼠牙周炎症及破骨细胞的影响

蔡烨华¹, 李星^2*, 赵艳霞³, 王丽⁴, 李航¹

1.邯郸市口腔医院牙周二科河北邯郸 056001;
2.石家庄市中医院口腔科,河北石家庄 050051;
3.邯郸市口腔医院牙体牙髓二科河北邯郸 056001;
4.邯郸市口腔医院儿童口腔科河北邯郸 056001

收稿日期:2024-04-10 出版日期:2024-11-28 发布日期:2024-11-27
通讯作者: *李星,E-mail:393117275@qq.com
作者简介:蔡烨华(1987~ ),女,河北邯郸人,本科,主治医师,主要从事口腔内科疾病的基础与临床研究。
基金资助:
河北省医学科学研究课题计划项目(编号:20230448)

Effects of Triptolide on Periodontal Inflammation and Osteoclasts in Orthodontic Tooth Movement Model Rats through p38 MAPK/ERK/JNK Signaling Pathway

CAI Yehua¹, LI Xing^2*, ZHAO Yanxia³, WANG Li⁴, LI Hang¹

1. Department of Periodontology, Handan Stomatological Hospital, Handan 056001, China;
2. Department of Stomatology, Shijiazhuang Traditional Chinese Medicine Hospital, Shijiazhuang 050051, China;
3. Department of Dentistry and Endodontics, Handan Stomatological Hospital, Handan 056001, China;
4. Department of Pediatric Dentistry, Handan Stomatological Hospital, Handan 056001, China

Received:2024-04-10 Online:2024-11-28 Published:2024-11-27

摘要/Abstract

摘要： 目的: 探究雷公藤甲素通过调控p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38 MAPK)/细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)/c-Jun氨基末端激酶(c-Jun amino-terminal kinase,JNK)信号通路对正畸牙移动模型大鼠牙周炎症及破骨细胞的影响。方法: 构建正畸牙移动大鼠模型,成功建模48只随机分成模型组、雷公藤甲素低(50 μg/kg)、高(100 μg/kg)剂量组、雷公藤甲素高剂量(100 μg/kg)+p38 MAPK激活剂(25 μg)组,每组12只;另设对照组(12只健康大鼠)。各组给予相应方法干预2周。测量正畸牙移动距离;抗酒石酸酸性磷酸酶染色观察牙周组织破骨细胞并进行计数;免疫组织化学染色法检测牙周组织骨形态发生蛋白-2(bone morphogenetic protein-2,BMP-2)表达强度;酶联免疫吸附法检测肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、前列腺素E2(prostaglandin E2,PGE2)、骨保护素(osteoprotegerin,OPG)、核因子-κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)水平;蛋白印迹法检测牙周组织p38 MAPK/ERK/JNK通路相关蛋白表达。结果: 与对照组相比,模型组正畸牙移动距离、牙周组织破骨细胞数目、BMP-2表达强度、血清TNF-α、IL-1β、PGE2、RANKL水平、磷酸化(phosphorylated,p)-p38 MAPK/p38 MAPK、p-ERK1/2/ERK1/2、p-JNK/JNK蛋白比值显著升高,血清OPG水平显著降低(P＜0.05);与模型组相比,雷公藤甲素低、高剂量组正畸牙移动距离、牙周组织BMP-2表达强度、血清OPG水平依次升高,牙周组织破骨细胞数目、血清TNF-α、IL-1β、PGE2、RANKL水平、p-p38 MAPK/p38 MAPK、p-ERK1/2/ERK1/2、p-JNK/JNK蛋白比值依次降低(P＜0.05);p38 MAPK激活剂可逆转高剂量雷公藤甲素对正畸牙移动模型大鼠的作用效果(P＜0.05)。结论: 雷公藤甲素可减轻正畸牙移动模型大鼠牙周炎症,降低破骨细胞数量,改善骨吸收,加速正畸牙移动,其机制与抑制p38 MAPK/ERK/JNK信号通路激活有关。

关键词: 雷公藤甲素, 正畸牙移动, 大鼠, 牙周组织, p38丝裂原活化蛋白激酶, 细胞外信号调节激酶, c-Jun氨基末端激酶

Abstract: Objective: To explore the effects of triptolide on periodontal inflammation and osteoclasts in orthodontic tooth movement model rats through regulating p38 mitogen-activated protein kinase (p38 MAPK)/extracellular signal-regulated kinase (ERK)/c-Jun amino-terminal kinase (JNK) signaling pathway. Methods: The rat orthodontic tooth model was established and totally 48 rats were randomly equally divided into model group, triptolide low dose (50 μg/kg) group, high dose (100 μg/kg) group, and triptolide high dose (100 μg/kg) + p38 MAPK activator (25 μg) group. Twelve healthy rats were set as control group. Each group was given corresponding intervention methods for 2 weeks. The distance of orthodontic tooth movement was measured. Osteoclasts in periodontal tissue were stained with tartrate resistant acid phosphatase and counted. The expression of bone morphogenetic protein-2 (BMP-2) in periodontal tissue was detected with immunohistochemical staining. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), prostaglandin E2 (PGE2), osteoprotegerin (OPG), and receptor activator of nuclear factor-κB ligand (RANKL) were detected by enzyme linked immunosorbent assay. The expressions of p38 MAPK/ERK/JNK pathway related proteins in periodontal tissues were detected by western blot. Results: Compared with control group, the movement distance of orthodontic teeth, the number of osteoclasts in periodontal tissue, the expression intensity of BMP-2, the levels of serum TNF-α, IL-1β, PGE2, RANKL, phosphorylated (p)-p38 MAPK/p38 MAPK, p-ERK1/2/ERK1/2, and p-JNK/JNK protein ratio in the model group were significantly increased, however, the serum OPG level was significantly decreased (P<0.05). Compared with model group, the movement distance of orthodontic teeth, the expression intensity of BMP-2 in periodontal tissue, and the level of serum OPG in triptolide low dose and high dose groups were increased successively, the number of osteoclasts in periodontal tissue, serum TNF-α, IL-1β, PGE2, RANKL levels, p-p38 MAPK/p38 MAPK, p-ERK1/2/ERK1/2, and p-JNK /JNK protein ratio were decreased (P<0.05). p38 MAPK activator could reverse the effect of high dose triptolide on orthodontic tooth movement model rats (P<0.05). Conclusion: Triptolide can reduce periodontal inflammation, decrease the number of osteoclasts, improve bone resorption, and accelerate orthodontic tooth movement in orthodontic model rats. Its mechanism is related to the inhibition of p38 MAPK/ERK/JNK signaling pathway activation.

Key words: triptolide, orthodontic tooth movement, rats, periodontal tissue, p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, c-Jun amino-terminal kinase

蔡烨华, 李星, 赵艳霞, 王丽, 李航. 雷公藤甲素调控p38 MAPK/ERK/JNK信号通路对正畸牙移动模型大鼠牙周炎症及破骨细胞的影响[J]. 口腔医学研究, 2024, 40(11): 978-984.

CAI Yehua, LI Xing, ZHAO Yanxia, WANG Li, LI Hang. Effects of Triptolide on Periodontal Inflammation and Osteoclasts in Orthodontic Tooth Movement Model Rats through p38 MAPK/ERK/JNK Signaling Pathway[J]. Journal of Oral Science Research, 2024, 40(11): 978-984.

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雷公藤甲素调控p38 MAPK/ERK/JNK信号通路对正畸牙移动模型大鼠牙周炎症及破骨细胞的影响

Effects of Triptolide on Periodontal Inflammation and Osteoclasts in Orthodontic Tooth Movement Model Rats through p38 MAPK/ERK/JNK Signaling Pathway

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