Possible Protective Effect of Diacerein on Inflammation-Induced Alveolar Bone Loss in Rats

雙醋瑞因對於發炎引致大白鼠齒槽骨破壞之可能保護效益初探

蘇冠瑋(Kwan-Wei Su) ； 黃仁勇(Ren-Yeong Huang) ； 陳仁焜(Jen-Kun Chen) ； 黃良吉(Liang-Gie Huang) ； 廖威能(Wei-Neng Liao) ； 蕭博元(Po-Yan Hsiao) ； 鄭琬蒨(Wan-Chien Cheng) ； 鍾其祥(Chi-Hsiang Chung) ； 黃寶賢(Po-Hsien Huang)

《臺灣牙周病醫學會雜誌》 21卷3期 (2016/09) Pp. 220-229

https://doi.org/10.6121/TAP.2016.21.3.03

摘要

牙周疾病是一盛行率極高之口腔疾病， 其主要的特徵在於牙齒支持組織(toothsupportingstructure)的破壞，晚近幾年的研究更發現，牙周病不只止限於對口腔產生危害，甚至可能威脅全身系統性疾病的嚴重性。蒽醌(anthraquinone)具有多種藥理及治療效果，其中的雙醋瑞因(diacerein, DAR)數十年以來的研究發現多半集中於對關節及其相關之組織或細胞的療效。然而，DAR對牙周病的治療潛力則尚未被研究及探討。本研究先以IC50 (half maximal inhibitory concentration)探討DAR對牙周致病菌P. gingivalis 與A. actinomycetemcomitans之抑菌能力及在大白鼠上顎第二大臼齒誘導產生實驗型牙周炎後之保護效果。實驗分組如下，雄性大白鼠分為3組，每組6隻動物：(1)動物沒有結紮線綑縛放置的空白對照組；(2)動物接受實驗型牙周炎誘導(結紮線綑縛放置)；以及(3)動物接受結紮線綑縛，同時口餵以DAR，劑量為50毫克／公斤／天。在第10天將動物犧牲，以供進一步分析和組織切片樣品製備。統計分析以one-way ANOVA以及Bonferronitest比較各組間的差異。結果顯示，DAR在低劑量 (12.5 μM)便可有效抑制牙周致病菌P.gingivalis與A. actinomycetemcomitans之生長，亦可在第10天改善實驗型牙周炎所產生之破壞(p ＜ 0.001)。另外組織形態學分析顯示，DAR治療可以減少牙周組織的嗜中性粒細胞浸潤(p ＜ 0.001)。這些研究結果表明，DAR極有可能在未來作為一輔助牙周病治療的選擇藥物。

關鍵字

實驗性牙周病模型 ； 蒽醌 ； 雙醋瑞因 ； 齒槽骨流失

並列摘要

Periodontal diseases are characterized by destruction of the tooth-supporting structure, and may be hazardous to general health. Diacerein (DAR), one derivatives from anthraquinone, has been shown to have a variety of pharmacological activities on joint-derived tissues/cells for decades. However, the therapeutic potential of anthraquinone on periodontal destruction has not yet been investigated. In the present study, we evaluated the effects of DAR on the growth of P. gingivalis and A. actinomycetemcomitans in vitro by determining the IC50 value, and on the periodontal disease induced by ligature placement on upper second molar in a rat model. Male Sprague-Dawley rats were divided into three groups (each group had six animals): (1) animals without ligature placement receiving 1.2% carboxymethyl cellulose (vehicle, control group); (2) animals with ligature placement receiving empty vehicle (ligation group); (3) animals with ligature receiving DAR (50 mg/kg/day, DAR group). The animals were sacrificed on day 10, and the tissue samples were prepared for further analysis. The oneway ANOVA analysis and Bonferroni test were used to test the difference among groups. The results demonstrated that DAR treatment at a low dose (12.5 μM) could suppress the growth of P. gingivalis and A. actinomycetemcomitans in a short time period, and the administration of DAR significantly ameliorated the periodontal destruction at Day 10 (p ＜ 0.001). Histomorphological analyses revealed that DAR treatment decreased the infiltration of polymorphonuclear cells in periodontal tissues (p ＜ 0.001). These findings suggest that diacerein could constitute a potential therapeutic drug to treat periodontal disease.

並列關鍵字

experimental periodontitis ； anthraquinone ； diacerein ； alveolar bone loss