诱导型一氧化氮合酶选择性抑制剂巯基乙基胍对大鼠结扎诱导性牙周炎的保护作用

Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat.

作者信息

Lohinai Z, Benedek P, Fehér E, Györfi A, Rosivall L, Fazekas A, Salzman A L, Szabó C

机构信息

Experimental Research Department and 2nd Institute of Physiology, Semmelweis Univ. Med. School, Budapest, Hungary.

出版信息

Br J Pharmacol. 1998 Feb;123(3):353-60. doi: 10.1038/sj.bjp.0701604.

DOI:10.1038/sj.bjp.0701604

PMID:9504374

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1565171/

Abstract

Excessive production of nitric oxide (NO), and the generation of peroxynitrite have been implicated in various proinflammatory conditions. In the present study, using mercaptoethylguanidine (MEG), a selective inhibitor of iNOS and a peroxynitrite scavenger, we investigated the role of iNOS and peroxynitrite in a rat model of periodontitis. 2. Periodontitis was produced in rat by a ligature of 2/0 braided silk placed around the cervix of the lower left 1st molar. Animals were then divided into two groups: one group of rats was treated with MEG (30 mg kg(-1), i.p., 4 times per day for 8 days), animals in the other group received vehicle. At day 8, the gingivomucosal tissue encircling the mandibular 1st molars was removed on both sides from ligated and sham operated animals for inducible nitric oxide synthase (iNOS) activity assay and for immunocytochemistry with anti-iNOS serum. Plasma extravasation was measured with the Evans blue technique. Alveolar bone loss was measured with a videomicroscopy. 3. Ligation caused a significant, more than 3 fold increase in the gingival iNOS activity, whereas it did not affect iNOS activity on the contralateral side, when compared to sham-operated animals. Immunohistochemical analysis revealed iNOS-positive macrophages, lymphocytes and PMNs in the connective tissue and immunoreactive layers of epithelium on side of the ligature, and only a few iNOS reactive connective tissue cells on the contralateral side [corrected]. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction compared to the contralateral side. MEG treatment significantly reduced the plasma extravasation and bone destruction. 4. The present results demonstrated that ligature-induced periodontitis increases local NO production and that MEG treatment protects against the associated extravasation and bone destruction. Based on the present data, we propose that enhanced formation of NO and peroxynitrite plays a significant role in the pathogenesis of periodontitis.

摘要

一氧化氮（NO）的过度产生以及过氧亚硝酸盐的生成与多种促炎状态有关。在本研究中，我们使用巯基乙胍（MEG），一种诱导型一氧化氮合酶（iNOS）的选择性抑制剂和过氧亚硝酸盐清除剂，研究了iNOS和过氧亚硝酸盐在大鼠牙周炎模型中的作用。2. 通过在左下第一磨牙颈部放置2/0编织丝线结扎在大鼠中诱发牙周炎。然后将动物分为两组：一组大鼠用MEG（30 mg kg⁻¹，腹腔注射，每天4次，共8天）治疗，另一组动物接受溶剂对照。在第8天，从结扎和假手术动物两侧切除环绕下颌第一磨牙的龈黏膜组织，用于诱导型一氧化氮合酶（iNOS）活性测定以及用抗iNOS血清进行免疫细胞化学分析。用伊文思蓝技术测量血浆外渗。用视频显微镜测量牙槽骨吸收。3. 与假手术动物相比，结扎导致牙龈iNOS活性显著增加，超过3倍，而对侧iNOS活性未受影响。免疫组织化学分析显示，结扎侧结缔组织和上皮免疫反应层中有iNOS阳性巨噬细胞、淋巴细胞和多形核中性粒细胞（PMN），而对侧只有少数iNOS反应性结缔组织细胞[校正后]。与对侧相比，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。MEG治疗显著减少了血浆外渗和骨破坏。4. 目前的结果表明，结扎诱导的牙周炎增加了局部NO的产生，并且MEG治疗可防止相关的外渗和骨破坏。基于目前的数据，我们认为NO和过氧亚硝酸盐的形成增强在牙周炎发病机制中起重要作用。