Di Paola R, Mazzon E, Muià C, Crisafulli C, Terrana D, Greco S, Britti D, Santori D, Oteri G, Cordasco G, Cuzzocrea S
Department of Clinical and Experimental Medicine and Pharmacology, Torre Biologica, Policlinico Universitario, Messina, Italy.
Br J Pharmacol. 2007 Feb;150(3):286-97. doi: 10.1038/sj.bjp.0706979. Epub 2007 Jan 2.
Etanercept is a tumour necrosis factor antagonist with anti-inflammatory effects. The aim of our study was to evaluate, for the first time, the therapeutic efficacy of in vivo inhibition of TNF-alpha in an experimental model of periodontitis.
Periodontitis was induced in adult male Sprague-Dawley rats by placing a nylon thread ligature around the lower 1st molars. Etanercept was administered at a dose of 5 mg kg-1, s.c., after placement of the ligature.
Periodontitis in rats resulted in an inflammatory process characterized by oedema, neutrophil infiltration and cytokine production that was followed by the recruitment of other inflammatory cells, production of a range of inflammatory mediators, tissue damage, apoptosis and disease. Treatment of the rats with etanercept (5 mg kg-1, s.c., after placement of the ligature) significantly reduced the degree of (1) periodontitis inflammation and tissue injury (histological score), (2) infiltration of neutrophils (MPO evaluation), (3) iNOS (the expression of nitrotyrosine and cytokines (eg TNF-alpha)) and (4) apoptosis (Bax and Bcl-2 expression).
Taken together, our results clearly demonstrate that treatment with etanercept reduces the development of inflammation and tissue injury, events associated with periodontitis.
依那西普是一种具有抗炎作用的肿瘤坏死因子拮抗剂。我们研究的目的是首次在牙周炎实验模型中评估体内抑制肿瘤坏死因子-α(TNF-α)的治疗效果。
通过在成年雄性斯普拉格-道利大鼠的下颌第一磨牙周围放置尼龙线结扎来诱导牙周炎。在结扎后,以5 mg/kg的剂量皮下注射依那西普。
大鼠牙周炎导致了一个以水肿、中性粒细胞浸润和细胞因子产生为特征的炎症过程,随后其他炎症细胞被募集,一系列炎症介质产生,组织损伤、细胞凋亡及疾病发生。用依那西普治疗大鼠(结扎后皮下注射5 mg/kg)显著降低了(1)牙周炎炎症和组织损伤程度(组织学评分),(2)中性粒细胞浸润(髓过氧化物酶评估),(3)诱导型一氧化氮合酶(硝基酪氨酸和细胞因子如TNF-α的表达),以及(4)细胞凋亡(Bax和Bcl-2表达)。
综上所述,我们的结果清楚地表明,依那西普治疗可减轻与牙周炎相关的炎症和组织损伤的发展。