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采用己酮可可碱进行预防和治疗性抗 TNF-α 治疗可减少关节炎及其相关牙周共病在小鼠中的发生。

Preventive and therapeutic anti-TNF-α therapy with pentoxifylline decreases arthritis and the associated periodontal co-morbidity in mice.

机构信息

Department of Oral Surgery and Pathology, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.

出版信息

Life Sci. 2013 Sep 17;93(9-11):423-8. doi: 10.1016/j.lfs.2013.07.022. Epub 2013 Aug 2.

Abstract

AIMS

The association between rheumatoid arthritis (RA) and periodontal disease (PD) has long been studied and some reports suggest that treating RA may improve the associated PD, and vice versa. This study aimed to evaluate the effects of an anti-tumor necrosis factor (TNF)-α therapy with pentoxifylline (PTX) in an experimental model of RA-associated PD.

MAIN METHODS

Male C57BL/6 mice were subjected to chronic antigen-induced arthritis (AIA) and daily treated with PTX (50mg/kg, i.p.) using preventive (Pre-PTX) or therapeutic (The-PTX) strategies. Fourteen days after the antigen challenge, mice were euthanized and knee joints, maxillae and serum were collected for microscopic and/or immunoenzymatic analysis.

KEY FINDINGS

AIA triggered significant leukocyte recruitment to the synovial cavity, tissue damage and proteoglycan loss in the knee joint. Pre-PTX and The-PTX regimens decreased these signs of joint inflammation. The increased levels of TNF-α and IL-17 in periarticular tissues of AIA mice were also reduced by both PTX treatments. Serum levels of C-reactive protein, which were augmented after AIA, were reduced by the PTX regimens. Concomitantly to AIA, mice presented alveolar bone loss, and recruitment of osteoclasts and neutrophils to periodontal tissues. Pre-PTX and The-PTX prevented and treated these signs of PD. PTX treatment also decreased TNF-α and increased IL-10 expression in the maxillae of AIA mice, although it did not affect the expression of IFN-γ and IL-17.

SIGNIFICANCE

The current study shows the anti-inflammatory and bone protective effects of preventive and therapeutic PTX treatments, which decreased the joint damage triggered by AIA and the associated periodontal co-morbidity.

摘要

目的

类风湿关节炎(RA)和牙周病(PD)之间的关联早已被研究,一些报告表明治疗 RA 可能会改善相关的 PD,反之亦然。本研究旨在评估在 RA 相关 PD 的实验模型中,使用五氧酚嗪(PTX)进行抗肿瘤坏死因子(TNF)-α治疗的效果。

主要方法

雄性 C57BL/6 小鼠接受慢性抗原诱导性关节炎(AIA),并用 PTX(50mg/kg,腹腔内)进行预防性(Pre-PTX)或治疗性(The-PTX)治疗。在抗原挑战后 14 天,处死小鼠并收集膝关节、上颌骨和血清,进行显微镜和/或免疫酶分析。

主要发现

AIA 引发了滑膜腔白细胞募集、膝关节组织损伤和蛋白聚糖丢失等明显的关节炎迹象。Pre-PTX 和 The-PTX 方案减少了这些关节炎症的迹象。PTX 治疗还降低了 AIA 小鼠周围组织中 TNF-α 和 IL-17 的升高水平。AIA 后血清 CRP 水平升高,PTX 方案也降低了 CRP 水平。同时,AIA 还导致了牙槽骨丢失,并伴有破骨细胞和中性粒细胞向牙周组织的募集。Pre-PTX 和 The-PTX 预防和治疗了这些 PD 迹象。PTX 治疗还降低了 AIA 小鼠上颌骨中的 TNF-α 并增加了 IL-10 的表达,但并未影响 IFN-γ 和 IL-17 的表达。

意义

本研究表明预防性和治疗性 PTX 治疗具有抗炎和骨保护作用,可减轻 AIA 引发的关节损伤和相关牙周共病。

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