干燥综合征为自身免疫性疾病，因存在泪腺和唾液腺功能障碍，可表现为口干、眼干。原发性干燥综合征患者唾液减少。因水的运动参与唾液分泌，水通道蛋白的表达、定位和功能已在唾液腺中广泛研究。迄今为止，AQP4是否存在于人类的唾液腺，目前仍然有争议。我们通过免疫组化、高分辨率显微镜和图像定量分析、Western blot和RT-PCR，鉴定正常对照组及原发性干燥综合征患者唾液腺活检中是否存在AQP4基因，同时明确AQP4蛋白分布。通过免疫组化分析，我们发现干燥综合征及正常对照组中，AQP4局限于腺泡基底部、闰管和纹状管侧面和顶部。最引人注目的结果为观察到AQP4定位于环绕腺泡小叶和闰管的肌上皮细胞(MEC)，且干燥综合征MEC中发现AQP4下调免疫反应。我们的研究结果提示，肌上皮细胞膜的跨膜水流能力在干燥综合征中可能改变。提示AQP4可能成为治疗口干的有前途的新治疗药物。

        附原文

        Abstract：A decreased saliva production occurs in primary Sjögren's syndrome(pSS), an autoimmune disease characterized by oral and ocular dryness due to dysfunction of the lacrimal and salivary glands (SGs). Since water movement is involved in saliva secretion, the expression, localization, and function of the water channels aquaporins (AQPs) have been extensively studied in SGs. To date, the presence of AQP4 remains controversial and ambiguous in human SGs. We investigated by immunohistochemistry, high-resolution confocal microscopy and quantitative image analysis, Western blot and real-time RT-PCR, the presence of the AQP4 gene, and the distribution of AQP4 protein in healthy controls and pSS SG biopsies. Through the immunohistochemical analysis, we demonstrated that AQP4 presence is confined to the basal region of acini, to the lateral and apical membrane of intercalated and striated ducts in both control and pSS glands. The most striking observation was the discovery of AQP4 localization in myoepithelial cells (MECs) that surround acini lobules and intercalated ducts, and the demonstration of AQP4-downregulated immunoreactivity in pSS MECs. Our studies suggest that the capacity for water flow across the membrane of MECs may be altered in pSS, identifying AQP4 as a promising new therapeutic agent to treat xerostomia.

        引自

        Sisto M,Lorusso L,Ingravallo G, et al. Abnormal distribution of AQP4 in minor salivary glands of primary Sjögren'ssyndromepatients.Autoimmunity.2017 Jun 24:1-9. doi: 10.1080/08916934.2017.1341495. [Epub ahead of print]