杜鹃素对结扎性牙周炎模型大鼠牙周组织损伤及mTOR/STAT3信号通路的影响  

Effects of Farrerol on Periodontal Tissue Injury and mTOR/STAT3 Signaling Pathway in Rats With Ligation Periodontitis

作　　者：唐小雪 李启期 高芸[1] 冒蕾 缑小蕊 金珊 TANG Xiaoxue;LI Qiqi;GAO Yun;MAO Lei;GOU Xiaorui;JIN Shan(Department of Stomatology,First Affiliated Hospital of Shihezi University,Shihezi 832008,China;Department of Pathology,First Affiliated Hospital of Shihezi University,Shihezi 832008,China)

机构地区：[1]石河子大学第一附属医院口腔科,新疆石河子832008 [2]石河子大学第一附属医院病理科,新疆石河子832008

出　　处：《中国药学杂志》2023年第24期2252-2258,共7页Chinese Pharmaceutical Journal

基　　金：2019年度自主资助支持石河子大学科研项目资助(ZZZC201957A)。

摘　　要：目的探讨杜鹃素对牙颈部结扎诱导的牙周炎大鼠牙周组织损伤的保护作用。方法将30只大鼠分为对照组、模型组、杜鹃素(45 mg·kg^(-1)·d^(-1))组、多西环素(20 mg·kg^(-1)·d^(-1))组、杜鹃素+哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)激动剂MHY1485(10 mg·kg^(-1)·d^(-1))组,牙颈部结扎法诱导牙周炎模型。通过微型计算机断层扫描(Micro-CT)分析牙槽骨丢失;酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测血清白细胞介素(interleukin,IL)-1β、IL-6和肿瘤坏死因子-α(tumor necrosis factorα,TNF-α)水平;苏木精-伊红(hematoxylin-eosin,HE)染色观察牙周组织病理学变化;抗酒石酸酸性磷酸酶(tartrate-resistant acid phosphatase,TRAP)染色检测破骨细胞形成情况;Western blot检测牙周组织中mTOR、信号转导和转录激活因子3(signal transducers and activators of transcription 3,STAT3)及其磷酸化蛋白水平。结果与对照组相比,模型组骨体积分数降低,釉牙骨质界(cemento-enamel junction,CEJ)-牙槽骨嵴(alveolar bone crest,ABC)距离、血清IL-1β、IL-6、TNF-α水平、组织病理学评分和破骨细胞形成数量以及p-mTOR/mTOR、p-STAT3/STAT3比值升高(均P<0.05)。与模型组比较,杜鹃素组和多西环素组骨体积分数升高,CEJ-ABC距离、IL-1β、IL-6、TNF-α水平、组织病理学评分和破骨细胞形成数量以及p-mTOR/mTOR、p-STAT3/STAT3比值降低(均P<0.05)。MHY1485可减弱杜鹃素对牙周炎大鼠牙槽骨吸收和炎症反应的抑制作用。结论杜鹃素可能通过抑制mTOR/STAT3信号通路抑制牙周炎症和破骨细胞生成,减轻牙周炎大鼠牙槽骨吸收。OBJECTIVE To investigate the protective effect of farrerol on periodontal tissue damage in rats with periodontitis induced by cervical ligation,and analyze the potential mechanism.METHODS Thirty rats were divided into control group,model group,farrerol group(45 mg·kg^(-1)·d^(-1)),doxycycline group(20 mg·kg^(-1)·d^(-1)),and farrerol+mammalian target of rapamycin(mTOR)agonist MHY1485(10 mg·kg^(-1)·d^(-1))group.Periodontitis model was induced by cervical ligation.Micro-computed tomography(Micro-CT)was used to analyze alveolar bone loss;the levels of serum interleukin(IL)-1β,IL-6 and tumor necrosis factor(TNF)-α were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of periodontal tissue.Tartrate-resistant acid phosphatase(TRAP)staining was used to detect the formation of osteoclasts.The levels of mTOR,signal transducers and activators of transcription 3(STAT3)and their phosphorylated proteins in periodontal tissue were detected by Western blot.RESULTS Compared with the control group,the bone volume fraction of the model group was significantly decreased,the distance from cemento-enamel junction(CEJ)to alveolar bone crest(ABC),the serum levels of IL-1β,IL-6,and TNF-α,histopathological score,osteoclast formation number,p-mTOR/mTOR,p-STAT3/STAT3 ratio were significantly increased(all P<0.05).Compared with the model group,the bone volume fraction was increased,and the CEJ-ABC distance,IL-1β,IL-6,TNF-αlevels,histopathological score,osteoclast formation number,p-mTOR/mTOR ratio,and p-STAT3/STAT3 ratio were decreased in the farrerol group and doxycycline group(all P<0.05).MHY1485 could attenuate the inhibitory effect of farrerol on alveolar bone resorption and inflammation in rats with periodontitis.CONCLUSION Farrerol may inhibit periodontal inflammation and osteoclast generation by inhibiting the mTOR/STAT3 signaling pathway,and reduce alveolar bone resorption in rats with periodontitis.

关 键 词：牙周炎 杜鹃素 哺乳动物雷帕霉素靶蛋白 信号转导 转录激活因子3 牙槽骨吸收 

分 类 号：R285.5[医药卫生—中药学] R966[医药卫生—中医学]