Department of Oral-facial Disorders, Osaka University Graduate School of Dentistry, Osaka, Japan.
Division for Clinical Laboratory, Osaka University Dental Hospital, Osaka, Japan.
Biochem Biophys Res Commun. 2018 Sep 5;503(2):1098-1102. doi: 10.1016/j.bbrc.2018.06.125. Epub 2018 Jul 3.
Hypofunction of the salivary gland causes several life-disrupting side effects such as dental caries, oral candidiasis, loss of taste, and swallowing disorders. No satisfactory therapy has been established to treat salivary hypofunction. Pilocarpine represents a potential treatment for dry mouth due to Sjögren's syndrome (SS). Although subjective improvement was consistently observed with pilocarpine therapy, the mechanism was unclear. In this study, we investigated the mechanism of recovery in salivation following treatment with pilocarpine. We first examined the effectiveness of pilocarpine in SS patients as quantified by the Saxon test and the visual analogue scale average. We found that salivation ability and subjective symptoms improved by continuous administration of pilocarpine. These results demonstrated that long-term medication for dry mouth patients was more effective. However, as the mechanism remained unclear, molecular biological mechanisms were analyzed based on the effects of continuous administration of pilocarpine using model mice. In the molecular biological analysis, continuous administration of pilocarpine was effective in both ICR and SS model mice. Gene and protein expression of muscarinic acetylcholine receptor 3 (M3R) increased in salivary glands following continuous administration of pilocarpine compared with single administration. Therefore, continuous administration of pilocarpine effectively induced M3R expression, thereby activating salivation.
唾液腺功能低下会导致多种扰乱生活的副作用，如龋齿、口腔念珠菌病、味觉丧失和吞咽障碍。目前尚无令人满意的疗法可用于治疗唾液腺功能低下。毛果芸香碱由于干燥综合征（SS）而代表了一种治疗口干的潜在疗法。尽管毛果芸香碱治疗始终观察到主观改善，但机制尚不清楚。在这项研究中，我们研究了毛果芸香碱治疗后唾液分泌恢复的机制。我们首先通过 Saxon 测试和视觉模拟量表平均评估检查了毛果芸香碱在 SS 患者中的有效性。我们发现，通过持续给予毛果芸香碱，唾液分泌能力和主观症状得到改善。这些结果表明，长期为口干患者服用药物更有效。然而，由于机制仍不清楚，因此基于使用模型小鼠的毛果芸香碱连续给药的效果进行了分子生物学机制分析。在分子生物学分析中，连续给予毛果芸香碱对 ICR 和 SS 模型小鼠均有效。与单次给药相比，连续给予毛果芸香碱后，唾液腺中毒蕈碱乙酰胆碱受体 3（M3R）的基因和蛋白表达增加。因此，连续给予毛果芸香碱可有效诱导 M3R 表达，从而激活唾液分泌。
