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

作　　者：蔡烨华 李星 赵艳霞 王丽 李航 CAI Yehua;LI Xing;ZHAO Yanxia;WANG Li;LI Hang(Department of Periodontology,Handan Stomatological Hospital,Handan 056001,China;Department of Stomatology,Shijiazhuang Traditional Chinese Medicine Hospital,Shijiazhuang 050051,China;Department of Dentistry and Endodontics,Handan Stomatological Hospital,Handan 056001,China;Department of Pediatric Dentistry,Handan Stomatological Hospital,Handan 056001,China)

机构地区：[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

出　　处：《口腔医学研究》2024年第11期978-984,共7页Journal of Oral Science Research

基　　金：河北省医学科学研究课题计划项目(编号:20230448)。

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(50μg/kg)、高(100μg/kg)剂量组、雷公藤甲素高剂量(100μg/kg)+p38 MAPK激活剂(25μg)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(50μg/kg)group,high dose(100μg/kg)group,and triptolide high dose(100μg/kg)+p38 MAPK activator(25μg)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 rati

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 

分 类 号：R783.5[医药卫生—口腔医学] R-332[医药卫生—临床医学]