Han Lichi, Wang Lei, Zhang Fuyin, Liu Ke Jian, Xiang Bin
a Department of Oral Medicine and Medical Research Center, Medical College, Dalian University, Dalian 116622, P.R. China;
b Department of Oral and Maxillofacial Surgery, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, P.R. China; and.
Radiat Res. 2015 Jun;183(6):693-700. doi: 10.1667/RR13890.1. Epub 2015 May 7.
Radiotherapy for malignant tumors of the head and neck commonly leads to radiation-induced sialadenitis as a result of radiation-induced salivary gland dysfunction. We demonstrated previously that phenylephrine could protect the irradiated submandibular gland against apoptosis, although the mechanism is unclear. In this study, we investigated the influence of phenylephrine pretreatment on the expressions of aquaporin 5 (AQP5) and c-Jun N-terminal kinase (JNK) that were presumed to have a role in radiation-induced salivary gland dysfunction. Rats pretreated with phenylephrine (5 mg/kg) were locally irradiated (20 Gy) in the head and neck region. The submandibular glands were removed on day 7 after irradiation. The expression of AQP5 and activation of JNK were measured by immunohistochemistry and Western blot. The localization of AQP5 at the apical and lateral plasma membrane of acinar cells was significantly reduced by irradiation, but markedly enhanced with phenylephrine pretreatment. The protein expression of AQP5 was decreased by 84.91% in irradiated glands, whereas it was fully recovered to the control level in phenylephrine-pretreated glands. Moreover, many acinar, ductal and granular convoluted tubular cells in the irradiated glands exhibited intense immunoreactivity for p-JNK, while in the phenylephrine-pretreated irradiated glands, only a few acinar cells exhibited very faint immunoreactivity for p-JNK. The protein expression level of p-JNK was increased by 41.65% in the irradiated alone glands, but was significantly decreased in the phenylephrine-pretreated irradiated glands. These results suggest that the protective mechanism of phenylephrine might be related to the improved expression of AQP5 and decreased activation of JNK. Pretreatment with phenylephrine in patients undergoing radiotherapy may provide a helpful strategy for suppression of radiation-induced sialadenitis.
头颈部恶性肿瘤的放射治疗通常会因辐射诱导的唾液腺功能障碍而导致放射性涎腺炎。我们之前已证明去氧肾上腺素可保护受照射的下颌下腺免于凋亡，但其机制尚不清楚。在本研究中，我们调查了去氧肾上腺素预处理对水通道蛋白5（AQP5）和c-Jun氨基末端激酶（JNK）表达的影响，推测这两者在辐射诱导的唾液腺功能障碍中起作用。用去氧肾上腺素（5mg/kg）预处理的大鼠在头颈部区域接受局部照射（20Gy）。照射后第7天切除下颌下腺。通过免疫组织化学和蛋白质印迹法测量AQP5的表达和JNK的激活情况。照射使腺泡细胞顶端和侧面质膜处的AQP5定位显著减少，但去氧肾上腺素预处理可使其明显增强。照射腺体中AQP5的蛋白表达下降了84.91%，而在去氧肾上腺素预处理的腺体中其完全恢复到对照水平。此外，照射腺体中的许多腺泡、导管和颗粒曲管细胞对p-JNK表现出强烈的免疫反应性，而在去氧肾上腺素预处理的照射腺体中，只有少数腺泡细胞对p-JNK表现出非常微弱的免疫反应性。单独照射的腺体中p-JNK的蛋白表达水平增加了41.65%，但在去氧肾上腺素预处理的照射腺体中显著降低。这些结果表明，去氧肾上腺素的保护机制可能与AQP5表达的改善和JNK激活的减少有关。对头颈部放疗患者进行去氧肾上腺素预处理可能为抑制放射性涎腺炎提供一种有用的策略。
