头颈癌是癌症诊断中的重要类型，其中在世界某些地区头颈癌的发病率正在上升。早期头颈癌的典型治疗方式包括手术或放疗，但是晚期病例通常需要手术后接受放射治疗和化疗。放疗后导致腮腺损伤会出现严重和慢性低功能性唾液分泌减少、口干燥、咀嚼和吞咽能力下降、发展口腔粘膜炎的风险增加和营养不良。目前还没有针对放射引起的唾液腺功能障碍的标准护理，治疗通常限于提供仅能提供暂时缓解的姑息治疗。腺苷酸单磷酸激酶（AMPK）是一种能够激活分解代谢过程并已被证明影响细胞周期、增殖和自噬的酶。在目前的研究中，我们发现放疗（IR）治疗会降低放疗后组织中磷酸化AMPK的水平，降低胞内NAD+和AMP的水平，增加胞内三磷酸腺苷的水平。此外，在放疗后5天，SIRT1和NAMPT的表达量较低。使用AMPK激活剂5-氨基咪唑-4-羧酸核苷酸（AICAR）和二甲双胍进行治疗可以减轻放射后的代偿性增殖（第6、7和30天）并逆转慢性（第30天）放射后的唾液腺功能障碍。此外，使用二甲双胍或AICAR处理后，在受辐射的腮腺中，顶/底极性标记（磷酸化aPKCζT560阳性区域）和分化标志（淀粉酶阳性区域）的水平增加到与未经处理的对照组相似的水平。总体而言，这些数据表明AMPK可能是治疗放射性唾液腺损伤的新型治疗靶点。

Head and neck cancers represent a significant portion of cancer diagnoses, with head and neck cancer incidence increasing in some parts of the world. Typical treatment of early-stage head and neck cancers includes either surgery or radiotherapy; however, advanced cases often require surgery followed by radiation and chemotherapy. Salivary gland damage following radiotherapy leads to severe and chronic hypofunction with decreased salivary output, xerostomia, impaired ability to chew and swallow, increased risk of developing oral mucositis, and malnutrition. There is currently no standard of care for radiation-induced salivary gland dysfunction, and treatment is often limited to palliative treatment that provides only temporary relief. Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is an enzyme that activates catabolic processes and has been shown to influence the cell cycle, proliferation, and autophagy. In the present study, we found that radiation (IR) treatment decreases tissue levels of phosphorylated AMPK following radiation and decreases intracellular NAD+ and AMP while increasing intracellular adenosine triphosphate. Furthermore, expression of sirtuin 1 (SIRT1) and nicotinamide phosphoribosyl transferase (NAMPT) was lower 5 d following IR. Treatment with AMPK activators, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) and metformin, attenuated compensatory proliferation (days 6, 7, and 30) following IR and reversed chronic (day 30) salivary gland dysfunction post-IR. In addition, treatment with metformin or AICAR increased markers of apical/basolateral polarity (phosphorylated aPKCζT560-positive area) and differentiation (amylase-positive area) within irradiated parotid glands to levels similar to untreated controls. Taken together, these data suggest that AMPK may be a novel therapeutic target for treatment of radiation-induced salivary damage.