Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat
Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat
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DOI：
10.1038/sj.bjp.0701604
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发表时间：
1998-02-01
影响因子：
7.3
通讯作者：
Szabó, C
中科院分区：
文献类型：
--
作者：
Lohinai, Z;Benedek, P;Szabó, C
一氧化氮（NO）的过量产生和过氧亚硝酸盐的产生与各种促炎性疾病有关。在本研究中，使用巯基乙基胍（MEG），一种选择性的iNOS抑制剂和过氧亚硝酸盐清除剂，我们研究了iNOS和过氧亚硝酸盐在大鼠牙周炎模型中的作用。2牙周炎是通过将2/0编织丝结扎在大鼠左下第一磨牙的颈部周围而产生的。然后将动物分为两组：一组大鼠用MEG（30 mg/kg，i. p.，每天4次，持续8天），另一组动物接受媒介物。在第8天，从结扎和假手术动物的两侧去除包围下颌第一磨牙的牙龈粘膜组织，用于诱导型一氧化氮合酶（iNOS）活性测定和用抗iNOS血清进行免疫细胞化学。用伊文思蓝技术测定血浆外渗量。用视频显微镜测量牙槽骨丢失。3与假手术动物相比，结扎导致牙龈iNOS活性显著增加3倍以上，而对侧的iNOS活性没有影响。免疫组化显示，结扎侧结缔组织和上皮基底层中有iNOS阳性的巨噬细胞、淋巴细胞和中性粒细胞，而对侧仅有少量iNOS阴性的结缔组织细胞。结扎组牙龈粘膜组织伊文思蓝渗出量和牙槽骨破坏均较对侧明显增加。MEG治疗显著减少了血浆外渗和骨破坏。4目前的结果表明，结扎引起的牙周炎增加了局部NO的产生，MEG治疗可以防止相关的外渗和骨破坏。基于目前的数据，我们提出，增强形成NO和过氧亚硝酸盐在牙周炎的发病机制中起着重要的作用。
1 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 Ist 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 Ist 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 basal layers of epithelium on side of the ligature, and only a few iNOS-negative connective tissue cells on the contralateral side. 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.