Takeda Ienaka, Kizu Yasuhiro, Yoshitaka Okamoto, Saito Ichiro, Yamane Gen-Yuki
Department of Oral Medicine, Tokyo Dental College, Chiba, Japan.
Radiat Res. 2003 Apr;159(4):465-70. doi: 10.1667/0033-7587(2003)159[0465:pronoi]2.0.co;2.
In this study, we developed a murine model of xerostomia to elucidate the mechanism of radiation-induced salivary gland dysfunction and determined the levels of nitric oxide (NO) in the salivary glands to assess its involvement in the salivary dysfunction induced by radiation. In addition, an inhibitor of NO synthesis was administered to the model in vivo, and its effect on saliva secretion was investigated. Salivary gland irradiation at a dose of 15 Gy caused a significant decrease in secretion compared to unirradiated salivary glands. There were no marked differences between the irradiated mice and unirradiated mice in water or food consumption or in body weight changes. The NO levels in the cultured salivary gland epithelial cells were increased by treatment with a combination of interferon gamma (Ifng), interleukin 1-beta (Il1b), and tumor necrosis factor alpha (Tnfa). Irradiation increased the NO level in the salivary gland tissue. The presence of N(G)-monomethyl-l-arginine acetate (l-NMMA), an inhibitor of NO synthesis, caused a decrease in the NO level in cultured salivary gland tissues after irradiation. Administration of l-NMMA to irradiated mice improved saliva secretion. These results suggest that excessive production of NO induced by radiation is involved in the formation of radiation-induced xerostomia. The finding that administration of an inhibitor of NO synthesis ameliorated the dysfunction of irradiated salivary glands indicates that NO plays a role as a mediator of the dry mouth symptoms that occur after irradiation.
在本研究中，我们建立了一个口干症的小鼠模型，以阐明辐射诱导唾液腺功能障碍的机制，并测定唾液腺中一氧化氮（NO）的水平，以评估其在辐射诱导的唾液功能障碍中的作用。此外，将NO合成抑制剂在体内给予该模型，并研究其对唾液分泌的影响。与未照射的唾液腺相比，15 Gy剂量的唾液腺照射导致分泌显著减少。照射小鼠和未照射小鼠在水或食物消耗以及体重变化方面没有明显差异。用γ干扰素（Ifng）、白细胞介素1-β（Il1b）和肿瘤坏死因子α（Tnfa）联合处理可增加培养的唾液腺上皮细胞中的NO水平。照射增加了唾液腺组织中的NO水平。NO合成抑制剂N（G）-单甲基-L-精氨酸乙酸盐（l-NMMA）的存在导致照射后培养的唾液腺组织中NO水平降低。给照射小鼠施用l-NMMA可改善唾液分泌。这些结果表明，辐射诱导的NO过量产生参与了辐射诱导的口干症的形成。施用NO合成抑制剂可改善照射后唾液腺功能障碍这一发现表明，NO作为照射后出现的口干症状的介质发挥作用。
