停經對於根尖病變進展的影響

Abstract

根尖病變(Apical lesion)是一種主要由根管系統的微生物感染所引起的發炎性 疾病。在這種細菌引起的骨頭吸收病灶中，有許多細菌的病理機轉是由細菌內毒 素所調控的。其中單核細胞以及巨噬細胞是調控發炎反應的關鍵效應細胞類型之一。研究表明，巨噬細胞在根尖病變中的發病機理中起著至關重要的作用，並參 與觸發病變擴展。 Raloxifene hydrochloride 是新一代的選擇性動情激素受體調節劑 (selective estrogen-receptor modulator，簡稱 SERM)，用於停經後婦女骨質疏鬆症的預防與 治療。先前的研究已經證實出在發炎反應發生時所產生的一氧化氮會增加成骨細 胞凋亡，並增強噬骨細胞調控的骨吸收進而促進根尖病變的進展。然而，其中 Raloxifene 在此機轉中的抑制效果仍待闡明。 在本次研究中，透過西方點墨法以及細胞存活率分析法，以 Raloxifene 處理過 後的人類骨肉瘤細胞 (MG-63)，在 SNP 刺激下，觀察 Raloxifene 在此路徑上是否 具有抑制效果。最後，設計誘導根尖病變的大鼠模型，在經過標準的根管開創後 給予 Raloxifene 腹腔注射治療，利用影像學分析以及組織免疫染色去探討對於根 尖病變的癒合狀況。研究結果發現，MG-63 在 SNP 刺激下，使用 Raloxifene 處裡 過後的細胞存活率上升以及其 cleavage-PARP 蛋白質表現量會下降，表示 Raloxifene 的保護作用可以抑制細胞走向細胞凋亡。至於所選擇的路徑 ER-α、 ER-β 亦或是其他路徑，則尚待討論。

Apical lesion is an inflammatory disease mainly caused by microbial infection of the root canal system. In bone resorption lesions, many bacterial pathological mechanisms are affected by bacterial endotoxin. Monocytes and macrophages are the key cell types that regulate inflammation. Studies have shown that macrophages play a vital role in the pathogenesis of root apical lesions and participate in triggering lesion expansion. Raloxifene hydrochloride is a new generation of selective estrogen-receptor modulator (SERM), used for the prevention and treatment of osteoporosis in postmenopausal women. Previous studies have confirmed that nitric oxide produced during inflammation may increase osteoblast apoptosis and enhance bone resorption. However, the inhibitory effect of Raloxifene in this mechanism remains to be confirmed. The human osteosarcoma cells (MG-63) were randomly divided into control group, Raloxifene pretreatment group with different SNP concentration treatment. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was adopted to detect the viability of MG-63 cells in each group. Protein expression levels of PARP in each group of MG-63 cells were tested using the Western blotting. The rat model with induced apical lesion were also designed by exposing the pulp chamber to oral cavity and Raloxifene treatment was performed after standard root canal debridement, the healing of the apical lesion was investigated by imaging analysis and tissue immunostaining. These results indicate that the protective effect of Raloxifene can inhibit MG-63 cell apoptosis. As for which pathway to work, ER-α, ER-β, or others, we need more evidence to prove it.