Tissue Function-Reactive Oxygen Cross-talk in Oral Region : Its Pathopharmacological Analysis

口腔组织功能-活性氧串扰：其病理药理学分析

• 批准号: 06454529
• 负责人: OKABE Eiichiro
• 金额: $ 4.54万
• 依托单位: Kanagawa Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-06454529/
• 关键词: Free radicals; Calcium; Calcitonin gene-related peptide; Dental pulp; Signal transduction; Lingual artery; Vascular smooth muscle; 血管反応; スーパーオキシドラジカル; ヒドロキシルラジカル; 一重項酸素; CGRP; NANC神経; 筋小胞体; 一酸化窒素; 歯髄

The physiological importance of the oxygen free radical system was revealed by the discovery that activated neutrophils produce the superoxide anion radical (O_2^<・->). The O_2^<・-> cascade (producing H_2O_2 and hydroxylradical, HO・) established in basic chemistry stimulated investigators of reactive oxygen species in numerous pathophysiological processes. The first target of reactive oxygen species, generated in several pathological processes, is the vascular system. In this research project, we wished to investigate the mechanisms of the effect of reactive oxygen species on vascular smooth muscle at the cellular level.1. The HO・radical directly produces vasoconstriction in the dental pulp in dogs. This could be explained by the destruction of basally released endothelium-derived relaxing factor, possibly nitric oxide, and/or endothelial dysfunction. The selective effect of this radical on endothelium-dependent relaxation of pulpal vessels is supported by the finding that the increase … More in blood flow caused by a direct-acting, endothelium-independent dilator, nitroglycerin, but not by acetylcholine, was unaffected by the exposure to the HO・radical.2. We found that canine lingual artery are innervated by calcitonin gene-related peptide (CGRP)-containing vasodilator nerves. The HO・radical, rather than H_2O_2, to be the active agent in disturbance of CGRP-mediated neurogenic relaxiation, and it can be suggested that HO・can deplete endogenous CGRP localized prejunctionally and also damage CGRP-induced relaxation of canine lingual artery that is caused by activation of ATP-sensitive K^+ channels at postjunctional sites.3. We evaluated the effects of reactive oxygen species on contractions induced by caffeine, Ins (1,4,5) P_3 and noradrenaline (NA) in Staphylococcal alpha-toxin-permeabilized rabbit mesenteric artery. The pathway of Ca^<2+> release from sarcoplasmic reticulum (SR) dependent on Ins (1,4,5) P_3 is insensitive to O_2^<・->. Instead, caffeine-induced Ca^<2+> release mechanism may be susceptible to O_2^<・->, and H_2O_2, rather than O_2^<・-> and HO・, may be the active agent in the NA-induced contraction. The results obtained are also consistent with the view that the attenuation by H_2O_2 of the NA-induced contraction may be linked to the receptor-associated pathway of Ins (1,4,5) P_3 formation.We also assessed the effect of singlet oxygen (^1O_2) on vascular reactivity of rabbit mesenteric artery ring preparations. ^1O_2 generated from photolysis of rose bengal is the potent destracive oxygen.****. Endothelium-dependent relaxation is quite vulnerable to ^1O_2 is depresses NA-induced contraction possibly via alpha-adrenoceptor dysfunction.If the sequence of events during pathophysiological processes such as periodontitis in the vascular wall as well (especially in endothelial cells), it may lead to disturbances of regional blood flow, which may aggravate the tissue injury. Less

激活的中性粒细胞产生超氧阴离子自由基（O_2^<·->）的发现揭示了氧自由基系统的生理重要性。基础化学中建立的O_2^<·->级联（产生H_2O_2和羟基自由基，HO·）刺激了许多病理生理过程中活性氧的研究人员。在多种病理过程中产生的活性氧的第一个目标是血管系统。在本研究项目中，我们希望从细胞水平探讨活性氧对血管平滑肌的影响机制。 1． HO·自由基直接在狗的牙髓中产生血管收缩。这可以通过基础释放的内皮衍生舒张因子（可能是一氧化氮）的破坏和/或内皮功能障碍来解释。该自由基对内皮依赖性牙髓血管松弛的选择性作用得到了以下发现的支持：由直接作用的内皮依赖性扩张剂硝酸甘油（而非乙酰胆碱）引起的血流量增加不受暴露于 HO·自由基的影响。2。我们发现犬舌动脉由含有降钙素基因相关肽（CGRP）的血管舒张神经支配。 HO·自由基，而不是H_2O_2，是干扰CGRP介导的神经源性松弛的活性剂，并且可以表明HO·可以消耗交界前局部的内源性CGRP，并且还损害CGRP诱导的犬舌动脉松弛，这是由接合后位点的ATP敏感的K^+通道激活引起的。 3．我们评估了活性氧对咖啡因、Ins (1,4,5) P_3 和去甲肾上腺素 (NA) 在葡萄球菌 α 毒素透化的兔肠系膜动脉中引起的收缩的影响。肌浆网(SR)依赖于Ins(1,4,5) P_3释放Ca^<2+>的途径对O_2^<·->不敏感。相反，咖啡因诱导的 Ca^<2+> 释放机制可能对 O_2^<·-> 敏感，并且 H_2O_2，而不是 O_2^<·-> 和 HO·，可能是 NA 诱导收缩的活性剂。所得结果也与H_2O_2对NA诱导的收缩的减弱可能与Ins(1,4,5)P_3形成的受体相关途径有关的观点一致。我们还评估了单线态氧(^1O_2)对兔肠系膜动脉环制剂的血管反应性的影响。孟加拉玫瑰光解产生的^1O_2 是强效的破坏性氧气。****。内皮依赖性松弛很容易受到^1O_2的影响，可能通过α-肾上腺素受体功能障碍抑制NA诱导的收缩。如果牙周炎等病理生理过程中的事件顺序也发生在血管壁（尤其是内皮细胞），可能会导致局部血流紊乱，从而加剧组织损伤。较少的

项目成果

陶山直昭: "ヒスタミンのウサギ舌動脈収縮機構" 日本薬理学雑誌. 103・4. 175-186 (1994)

Naoaki Suyama：“组胺对兔舌动脉的收缩机制”《日本药理学杂志》103・4（1994）。

Dai Kobayashi: "Calcitonin gene-related peptide mediated neurogenic vasorelaxation in the isolated canine Iingual artery" Japanese Journal of Pharmacology. 64・4. 329-339 (1995)

Dai Kobayashi：“降钙素基因相关肽介导的离体犬舌动脉神经源性血管舒张”日本药理学杂志 64・4（1995）。

Sekishita, T.: "Endotoxin increases sensitivity of prejunctional muscarinic receptors in rabbit mesenteric artery" Bulletin of Kanagawa Dental College. 22. 8-17 (1994)

Sekishita, T.：“内毒素增加兔肠系膜动脉中交界前毒蕈碱受体的敏感性”神奈川牙科学院通报。

Todoki, K.: "Measurement of reactive oxygen species in a biological system and its perspectives" Folia Pharmacologica Japonica. 108. 295-306 (1996)

Todoki, K.：“生物系统中活性氧的测量及其前景”Folia Pharmacologica Japonica。

Wada, S.: "Effect of reactive oxygen species on reactivity of alpha-toxin-permeabilized rabbit mesenteric artery" Magnetic Resonance in Medicine. 7. 93-96 (1996)

Wada, S.：“活性氧对α-毒素透化兔肠系膜动脉反应性的影响”医学磁共振。