SALIVARY GLAND DYSFUNCTION IN AUTOIMMUNE NOD MICE

唾液腺功能障碍是由饮食变化、放射治疗、 衰老、某些药物以及病毒或遗传性疾病。损失的损失 腺体功能和唾液分泌导致临床 口干症或“口干”的表现。一些自身免疫性疾病 例如，人类患有干燥综合征和1型糖尿病(IDD) 进行性淋巴细胞性浸润性唾液腺 随之而来的唾液合成和分泌减少。国际直拨电话是 以自身免疫破坏产生胰岛素的β细胞为特征的 胰腺。进一步的研究表明，在糖尿病患者中 患者和NOD(非肥胖型糖尿病)小鼠，淋巴细胞浸润 外分泌组织，包括颌下腺，是很常见的。一 人类自身免疫性IDD的代谢并发症为口干症 龋病和潜在牙周病的相关增加 发展。到目前为止，开发一种合适的动物模型来研究 分析自身免疫引起的唾液腺功能障碍将有助于 口干症的研究。使用点头鼠标，我们最近观察到 伴随着针对β细胞、淋巴细胞的进行性自身免疫反应 同时渗入腮腺和颌下腺 糖尿病和糖尿病前期动物。这伴随着一份相应的 刺激流率下降和特定分泌蛋白的丢失 生物合成能力。这些观察表明唾液腺 功能障碍不是由于急性炎症反应引起的 淋巴细胞渗入和细胞破坏，但更准确地说 反映了由于慢性淋巴细胞激活而引起的变化 自身免疫病理学。因此，我们建议在这里调查 NOD小鼠自身免疫性涎腺炎的研究 自身免疫性口干症的动物模型。具体地说，我们计划 1)描述针对唾液腺的自身免疫反应导致 口干症；2)测定膜受体水平的变化和 信号转导通路的细胞内组件是 通常在分泌过程中被激活，并3)表征 胰岛素样肽对腮腺功能的影响 IDD患者的自身免疫性涎腺炎。这些研究的结果应该提供 对传统上导致唾液的自身免疫反应的洞察 腺体功能障碍具有明显的临床和牙科相关性。在……里面 此外，我们预计点头鼠标将被证明是一个有用的模型 加深对干燥综合征、类风湿性关节炎的认识 和1型IDD疾病，其中自身免疫病理导致 保护性唾液分泌物，导致患者不适 与口干症和龋齿增加、牙周病和 口腔粘膜和软组织加重。

Salivary gland dysfunction results from dietary changes, radiation therapy, aging, certain medications and viral or genetic diseases. The loss of gland function and thus saliva production results in the clinical manifestation of xerostomia or "dry mouth." Some autoimmune diseases of man, for example, Sjogrens syndrome and Type 1 diabetes (IDD), show progressive lymphocytic infiltration of the salivary glands with a subsequent reduction in saliva synthesis and secretion. IDD is characterized by autoimmune destruction of insulin producing beta cells of the pancreas. Further investigations have revealed that in diabetic patients and the NOD (non-obese diabetic) mouse, lymphocytic infiltration of exocrine tissues, including the submandibular gland, is common. One metabolic complication of human autoimmune IDD is xerostomia with associated increases in caries and potential periodontal disease development. To date, development of an adequate animal model for the analysis of autoimmune induced salivary gland dysfunction would facilitate the study of xerostomia. Using the NOD mouse, we recently observed that with the progressive autoimmune reaction against beta cells, lymphocytes simultaneously infiltrated into the parotid and submandibular glands of diabetic and pre-diabetic animals. This was accompanied by a corresponding decline in stimulated flow rates and loss of specific secretory protein biosynthetic capacity. These observations suggest that salivary gland dysfunction is not due to an acute inflammatory response caused by lymphocytic infiltration and cellular destruction, but more accurately reflects changes due to the chronic lymphocytic activation present in the autoimmune pathology. Therefore, we propose here to investigate the autoimmune sialoadenitis of the NOD mouse to determine its potential as an animal model for autoimmune-induced xerostomia. Specifically, we plan to 1) Characterize the autoimmune reaction against salivary glands leading to xerostomia; 2) Determine changes in the level of membrane receptors and intracellular components of the signal transduction pathways which are commonly activated during the secretory process and 3) Characterize the role of insulin-like peptides on parotid gland function at onset of autoimmune sialoadenitis in IDD. Results from these studies should provide insights into autoimmune responses that traditionally lead to salivary gland dysfunction with obvious clinical and dental relevance. In addition, we anticipate that the NOD mouse will prove to be a useful model for developing our understanding of Sjogrens syndrome, Rheumatoid arthritis and Type 1 IDD; diseases in which the autoimmune pathology causes a loss of protective salivary secretions with the resulting patient discomfort associated with xerostomia and increased caries, periodontal disease and aggravation of oral mucosa and soft tissue.