Lohinai Z, Stachlewitz R, Székely A D, Fehér E, Dézsi L, Szabó C
Institute of Human Physiology and Clinical Experimental Research, Semmelweis University, Budapest, Hungary.
Life Sci. 2001 Dec 7;70(3):279-90. doi: 10.1016/s0024-3205(01)01391-1.
We investigated the role of the inducible isoform of cyclooxygenase (COX-2) in a rat model of periodontitis using a selective COX-2 inhibitor NS-398. Periodontitis was produced by a silk ligature placed around the lower left 1st molar. Animals were treated with NS-398 (3 mg kg(-1) i.p., 2 times per day for 7 days) or vehicle. At Day 8, the gingivomucosal tissues encircling the mandibular 1st molars were removed on both sides for COX-2 immunohistochemistry, measurement of plasma extravasation by the Evans blue technique, and alveolar bone loss by videomicroscopy. Immunohistochemical analysis revealed numerous strongly COX-2-positive cells in the subepithelial tissues in the ligated side and only a few COX-2-reactive cells in the contralateral (control) side. Ligation significantly increased Evans blue extravasation in the gingivomucosal tissue and alveolar bone destruction compared to the control side. NS-398 treatment significantly reduced the plasma extravasation and alveolar bone resorption of the ligated side compared to vehicle administration. The present results suggest that COX-2 is induced by periodontitis, and plays an important role in gingival inflammation and alveolar bone destruction. In a previous study (Br J Pharmacol 1998;123:353-60) we found the expression of the inducible isoform of nitric oxide synthase in this model. Therefore, based on our own data and the literature, we propose that selective inhibition of these inducible enzymes might be a basis for adjunctive therapy, or new therapeutic approaches in periodontitis.
我们使用选择性环氧化酶-2(COX-2)抑制剂NS-398,在大鼠牙周炎模型中研究了诱导型COX-2的作用。通过在左下第一磨牙周围放置丝线结扎来诱发牙周炎。动物分别接受NS-398(3mg/kg腹腔注射,每天2次,共7天)或赋形剂处理。在第8天,切除双侧环绕下颌第一磨牙的龈黏膜组织,用于COX-2免疫组织化学检测、用伊文思蓝技术测量血浆外渗以及用视频显微镜观察牙槽骨吸收情况。免疫组织化学分析显示,结扎侧的上皮下组织中有大量强COX-2阳性细胞,而对侧(对照)只有少数COX-2反应性细胞。与对照侧相比,结扎显著增加了龈黏膜组织中的伊文思蓝外渗和牙槽骨破坏。与赋形剂给药相比,NS-398处理显著降低了结扎侧的血浆外渗和牙槽骨吸收。目前的结果表明,COX-2由牙周炎诱导产生,并在牙龈炎症和牙槽骨破坏中起重要作用。在之前的一项研究(《英国药理学杂志》1998年;123:353 - 60)中,我们在该模型中发现了一氧化氮合酶诱导型同工型的表达。因此,基于我们自己的数据和文献,我们提出选择性抑制这些诱导酶可能是牙周炎辅助治疗或新治疗方法的基础。