丁香油酚在牙槽骨组织中的骨保护作用评价
|
摘要
绝经后雌激素缺乏会引起牙槽骨质流失、重塑和炎症。丁香油酚是一种酚类化合物,在牙科应用广泛并具有抗炎特性。在本研究中,以卵巢切除的大鼠为模型,服用不同剂量丁香油酚(2mg·kg~(-1)·d~(-1)和4mg·kg~(-1)·d~(-1))12周(卵巢切除组),研究丁香油酚在牙槽骨组织中的骨保护作用。使用ELISA法检测血清中骨代谢标记物和促炎细胞因子,使用高分辨率微型计算机断层摄影术(CT)扫描牙槽骨形态,并进行骨组织学分析(H&E染色)。研究结果表明,丁香油酚不会增加卵巢切除大鼠体重和延缓子宫萎缩。由丁香油酚处理的卵巢切除大鼠的骨代谢标志物和炎性细胞因子含量显著提高,特别是高剂量组。丁香油酚的处理显著减弱了牙槽骨的形态测量变化,改善了牙槽吸收功能和牙龈渗透。卵巢切除大鼠的牙槽骨由于丁香油酚处理得到改善,炎性细胞因子表达降低。本研究初步结论表明,丁香油酚可以防止卵巢切除动物实验性诱导的牙槽骨损失,具有抗炎作用,对牙槽骨组织具有保护作用。
Postmenopausal estrogen deficiency causes alveolar bone loss, remodeling, and inflammation. Eugenol is a phenolic compound widely used in dentistry which has anti-inflammatory properties. In this study, the osteoprotective effect of eugenol on alveolar bone tissue was studied in ovariectomized rats that received different doses of eugenol(2 mg·kg~(-1)·d~(-1) and 4 mg·kg~(-1)·d~(-1)) for 12 weeks(the ovariectomized group). Serum markers of bone metabolism and proinflammatory cytokines were detected by ELISA, while alveolar bone morphology was scanned using high-resolution microcomputed tomography(CT) and bone histological analysis was performed by H&E staining. The results showed that eugenol did not increase weight or delay uterine atrophy in ovariectomized rats. The contents of bone metabolism markers and inflammatory cytokines in ovariectomized rats treated with eugenol were significantly increased, especially in the high-dose group. Eugenol treatment significantly reduced the morphometric changes of alveolar bone and improved alveolar absorption and gingival penetration. The expression of inflammatory cytokines was decreased in the alveolar bone of ovariectomized rats due to the improvement of eugenol treatment. The preliminary conclusion of this study indicates that eugenol can prevent the loss of alveolar bone, which is induced experimentally in ovariectomized animals, and has anti-inflammatory effect and protective effect on alveolar bone tissue.
Postmenopausal estrogen deficiency causes alveolar bone loss, remodeling, and inflammation. Eugenol is a phenolic compound widely used in dentistry which has anti-inflammatory properties. In this study, the osteoprotective effect of eugenol on alveolar bone tissue was studied in ovariectomized rats that received different doses of eugenol(2 mg·kg~(-1)·d~(-1) and 4 mg·kg~(-1)·d~(-1)) for 12 weeks(the ovariectomized group). Serum markers of bone metabolism and proinflammatory cytokines were detected by ELISA, while alveolar bone morphology was scanned using high-resolution microcomputed tomography(CT) and bone histological analysis was performed by H&E staining. The results showed that eugenol did not increase weight or delay uterine atrophy in ovariectomized rats. The contents of bone metabolism markers and inflammatory cytokines in ovariectomized rats treated with eugenol were significantly increased, especially in the high-dose group. Eugenol treatment significantly reduced the morphometric changes of alveolar bone and improved alveolar absorption and gingival penetration. The expression of inflammatory cytokines was decreased in the alveolar bone of ovariectomized rats due to the improvement of eugenol treatment. The preliminary conclusion of this study indicates that eugenol can prevent the loss of alveolar bone, which is induced experimentally in ovariectomized animals, and has anti-inflammatory effect and protective effect on alveolar bone tissue.
引文
Al-Sharif I.,Remmal A.,and Aboussekhra A.,2013,Eugenol triggers apoptosis in breast cancer cells through E2F1/survivin down-regulation,BMC Cancer,13(1):600
Barnhoorn I.E.,Bornman M.S.,Pieterse G.M.,and van Vuren J.H.,2004,Histological evidence of intersex in feral sharptooth catfish(Clarias gariepinus)from an estrogen-polluted water source in Gauteng,South Africa,Environ.Toxicol.19(6):603-608
Dai Q.,Zhang P.,Wu Y.Q.,Ma X.H.,Pang J.,Jiang L.Y.,and Fang B.,2014,Ovariectomy induces osteoporosis in the maxillary alveolar bone:an in vivo micro-CT and histomorphometric analysis in rats,Oral Dis.,20(5):514-520
Dutt P.,Chaudhary S.R.,and Kumar P.,2013,Oral health and menopause:A comprehensive review on current knowledge and associated dental management,Ann.Med.Health Sci.Res.,3(3):320-323
Esmaeili F.,Rajabnejhad S.,Partoazar A.R.,Mehr S.E.,Faridi-Majidi R.,Sahebgharani M.,Syedmoradi L.,Rajabnejhad M.R.,and Amani A.,2015,Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system,Pharm Dev.Technol.,21(7):887-893
Fonsêca D.V.,Salgado P.R.,Neto H.C.A.,Golzio A.M.,Caldas Filho M.R.,Melo C.G.,Leite F.C.,Piuvezam M.R.,Pordeus L.C.,Barbosa Filho J.M.,and Almeida R.N.,2016,Orthoeugenol exhibits anti-nociceptive and anti-inflammatory activities,Int.Immunopharmacol.,38:402-408
Geary N.,Asarian L.,Korach K.S.,Pfaff D.W.,and Ogawa S.2001,Deficits in E2-dependent control of feeding,weight gain,and cholecystokinin satiation in ER-alpha null mice,Endocrinology,142(11):4751-4757
Jia Z.,Zhang F.W.,Qi X.Y.,Yan X.,Hua Y.,Zhao M.M.,and Liu DY.,2017,Effect of estrogen deficiency on the expression levels of nuclear factor-kappa B and interleukin-17 in periodontal tissues,Zhongguo Zuzhi Gongcheng Yanjiu(Chinese Journal of Tissue Engineering Research),21(24):3796-3802(贾智,张丰伟,祁星颖,闫潇,华烨,赵梦明,刘大勇,2017雌激素缺乏状态下牙周组织中核转录因子κB及白细胞介素17的表达变化,中国组织工程研究,21(24):3796-3802)
Kim M.K.,Kim H.D.,Park J.H.,Lim J.I.,Yang J.S.,Kwak W.Y.Sung S.Y.,Kim H.J.,Kim S.H.,Lee C.H.,Shim J.Y.,Bae M.H.,Shin Y.A.,Huh Y.,Han T.D.,Chong W.,Choi H.Ahn B.N.,Yang S.O.,and Son M.H.,2006,An orally active cathepsin K inhibitor,furan-2-carboxylic acid,1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl-cyclohexyl)-amide(OST-4077),inhibits osteoclast activity in vitro and bone loss in ovariectomized rats J.Pharmacol.Exp.Ther.,318(2):555-562
Krall E.A.,Dawson-Hughes B.,Hannan M.T.,Wilson P.W.,and Kiel D.P.,1997,Postmenopausal estrogen replacement and tooth retention,Am.J.Med.,102(6):536-542
Luo K.,Ma S.,Guo J.,Huang Y.,Yan F.,and Xiao Y.,2014,Association between postmenopausal osteoporosis and experimental periodontitis,Biomed.Res.Int.,5:316134
Mnafgui K.,Hajji R.,Derbali F.,Gammoudi A.,Khabbabi G.,Ellefi H.,Allouche N.,Kadri A.,and Gharsallah N.,2015,Anti-inflammatory,antithrombotic and cardiac remodeling preventive effects of eugenol in isoproterenol-induced myocardial infarction in wistar rat,Cardiovasc.Toxicol.,16(4):336-344
魻ztürk H.魻.A.,2005,The anti-inflammatory activity of Eugenia caryophyllata essential oil:An animal model of anti-inflammatory activity,European Journal of General Medicine,2(4):1619-1622
Palumbo C.,Ferretti M.,Bertoni L.,Cavani F.,Resca E.,Casolari B.,Carnevale G.,Zavatti M.,Montanari C.,Benelli A.,and Zanoli P.,2009,Influence of ferutinin on bone metabolism in ovariectomized rats.I:role in preventing osteoporosis,J.Bone Miner.Metab.,27(5):538-545
Taguchi A.,Suei Y.,Ohtsuka M.,Otani K.,Tanimoto K.,and O-htaki M.,1996,Usefulness of panoramic radiography in the diagnosis of postmenopausal osteoporosis in women.Width and morphology of inferior cortex of the mandible,Dentomaxillofacial Radiol.,25(5):263-267
Tanaka M.,Toyooka E.,Kohno S.,Ozawa H.,and Ejiri S.,2003,Long-term changes in trabecular structure of aged rat alveolar bone after ovariectomy,Oral Surg.Oral Med.Oral Pathol.Oral Rad.Endod.,95(4):495-502
Yang J.,Farnell D.,Devlin H.,Horner K.,and Graham J.,2005,The effect of ovariectomy on mandibular cortical thickness in the rat,J.Dent.,33(2):123-129
Yu H.P.,Wu K.G.,Wu T.R.,Zhong S.S.,Chai X.H.,and Li Z.H.,2009,Clove essential oil extracting by SFE-MD or refluxing and its GC-MS analyzed,Shipin Yu Fajiao Gongye(Food and Fermentation Industries),35(1):145-149(于泓鹏,吴克刚,吴彤锐,钟少枢,柴向华,李泽洪,2009,丁香精油的超临界CO2和溶剂回流萃取及其GC-MS分析,食品与发酵工业,35(1):145-149)
Zhu D.Y.,Lv Y.,and Zhen Q.T.,2003,Isolation of eugenol from volatile oil of cloves by inclusion method,Zhongcaoyao(Chinese Traditional and Herbal Drugs),34(7):582-584(朱德裕,吕扬,郑启泰,2003,丁香油酚的包结分离研究,中草药,34(7):582-584)
Zin W.A.,Silva A.G.,Magalhāes C.B.,Carvalho G.M,Riva D.R.,Lima C.C.,Leal-Cardoso J.H.,Takiya C.M.,Valen?a S.S.,Saldiva P.H.,and Faffe D.S.,2012,Eugenol attenuates pulmonary damage induced by diesel exhaust particles,J.App.Physiol.,112(5):911
Barnhoorn I.E.,Bornman M.S.,Pieterse G.M.,and van Vuren J.H.,2004,Histological evidence of intersex in feral sharptooth catfish(Clarias gariepinus)from an estrogen-polluted water source in Gauteng,South Africa,Environ.Toxicol.19(6):603-608
Dai Q.,Zhang P.,Wu Y.Q.,Ma X.H.,Pang J.,Jiang L.Y.,and Fang B.,2014,Ovariectomy induces osteoporosis in the maxillary alveolar bone:an in vivo micro-CT and histomorphometric analysis in rats,Oral Dis.,20(5):514-520
Dutt P.,Chaudhary S.R.,and Kumar P.,2013,Oral health and menopause:A comprehensive review on current knowledge and associated dental management,Ann.Med.Health Sci.Res.,3(3):320-323
Esmaeili F.,Rajabnejhad S.,Partoazar A.R.,Mehr S.E.,Faridi-Majidi R.,Sahebgharani M.,Syedmoradi L.,Rajabnejhad M.R.,and Amani A.,2015,Anti-inflammatory effects of eugenol nanoemulsion as a topical delivery system,Pharm Dev.Technol.,21(7):887-893
Fonsêca D.V.,Salgado P.R.,Neto H.C.A.,Golzio A.M.,Caldas Filho M.R.,Melo C.G.,Leite F.C.,Piuvezam M.R.,Pordeus L.C.,Barbosa Filho J.M.,and Almeida R.N.,2016,Orthoeugenol exhibits anti-nociceptive and anti-inflammatory activities,Int.Immunopharmacol.,38:402-408
Geary N.,Asarian L.,Korach K.S.,Pfaff D.W.,and Ogawa S.2001,Deficits in E2-dependent control of feeding,weight gain,and cholecystokinin satiation in ER-alpha null mice,Endocrinology,142(11):4751-4757
Jia Z.,Zhang F.W.,Qi X.Y.,Yan X.,Hua Y.,Zhao M.M.,and Liu DY.,2017,Effect of estrogen deficiency on the expression levels of nuclear factor-kappa B and interleukin-17 in periodontal tissues,Zhongguo Zuzhi Gongcheng Yanjiu(Chinese Journal of Tissue Engineering Research),21(24):3796-3802(贾智,张丰伟,祁星颖,闫潇,华烨,赵梦明,刘大勇,2017雌激素缺乏状态下牙周组织中核转录因子κB及白细胞介素17的表达变化,中国组织工程研究,21(24):3796-3802)
Kim M.K.,Kim H.D.,Park J.H.,Lim J.I.,Yang J.S.,Kwak W.Y.Sung S.Y.,Kim H.J.,Kim S.H.,Lee C.H.,Shim J.Y.,Bae M.H.,Shin Y.A.,Huh Y.,Han T.D.,Chong W.,Choi H.Ahn B.N.,Yang S.O.,and Son M.H.,2006,An orally active cathepsin K inhibitor,furan-2-carboxylic acid,1-{1-[4-fluoro-2-(2-oxo-pyrrolidin-1-yl)-phenyl]-3-oxo-piperidin-4-ylcarbamoyl-cyclohexyl)-amide(OST-4077),inhibits osteoclast activity in vitro and bone loss in ovariectomized rats J.Pharmacol.Exp.Ther.,318(2):555-562
Krall E.A.,Dawson-Hughes B.,Hannan M.T.,Wilson P.W.,and Kiel D.P.,1997,Postmenopausal estrogen replacement and tooth retention,Am.J.Med.,102(6):536-542
Luo K.,Ma S.,Guo J.,Huang Y.,Yan F.,and Xiao Y.,2014,Association between postmenopausal osteoporosis and experimental periodontitis,Biomed.Res.Int.,5:316134
Mnafgui K.,Hajji R.,Derbali F.,Gammoudi A.,Khabbabi G.,Ellefi H.,Allouche N.,Kadri A.,and Gharsallah N.,2015,Anti-inflammatory,antithrombotic and cardiac remodeling preventive effects of eugenol in isoproterenol-induced myocardial infarction in wistar rat,Cardiovasc.Toxicol.,16(4):336-344
魻ztürk H.魻.A.,2005,The anti-inflammatory activity of Eugenia caryophyllata essential oil:An animal model of anti-inflammatory activity,European Journal of General Medicine,2(4):1619-1622
Palumbo C.,Ferretti M.,Bertoni L.,Cavani F.,Resca E.,Casolari B.,Carnevale G.,Zavatti M.,Montanari C.,Benelli A.,and Zanoli P.,2009,Influence of ferutinin on bone metabolism in ovariectomized rats.I:role in preventing osteoporosis,J.Bone Miner.Metab.,27(5):538-545
Taguchi A.,Suei Y.,Ohtsuka M.,Otani K.,Tanimoto K.,and O-htaki M.,1996,Usefulness of panoramic radiography in the diagnosis of postmenopausal osteoporosis in women.Width and morphology of inferior cortex of the mandible,Dentomaxillofacial Radiol.,25(5):263-267
Tanaka M.,Toyooka E.,Kohno S.,Ozawa H.,and Ejiri S.,2003,Long-term changes in trabecular structure of aged rat alveolar bone after ovariectomy,Oral Surg.Oral Med.Oral Pathol.Oral Rad.Endod.,95(4):495-502
Yang J.,Farnell D.,Devlin H.,Horner K.,and Graham J.,2005,The effect of ovariectomy on mandibular cortical thickness in the rat,J.Dent.,33(2):123-129
Yu H.P.,Wu K.G.,Wu T.R.,Zhong S.S.,Chai X.H.,and Li Z.H.,2009,Clove essential oil extracting by SFE-MD or refluxing and its GC-MS analyzed,Shipin Yu Fajiao Gongye(Food and Fermentation Industries),35(1):145-149(于泓鹏,吴克刚,吴彤锐,钟少枢,柴向华,李泽洪,2009,丁香精油的超临界CO2和溶剂回流萃取及其GC-MS分析,食品与发酵工业,35(1):145-149)
Zhu D.Y.,Lv Y.,and Zhen Q.T.,2003,Isolation of eugenol from volatile oil of cloves by inclusion method,Zhongcaoyao(Chinese Traditional and Herbal Drugs),34(7):582-584(朱德裕,吕扬,郑启泰,2003,丁香油酚的包结分离研究,中草药,34(7):582-584)
Zin W.A.,Silva A.G.,Magalhāes C.B.,Carvalho G.M,Riva D.R.,Lima C.C.,Leal-Cardoso J.H.,Takiya C.M.,Valen?a S.S.,Saldiva P.H.,and Faffe D.S.,2012,Eugenol attenuates pulmonary damage induced by diesel exhaust particles,J.App.Physiol.,112(5):911