Burlage Fred R, Faber Hette, Kampinga Harm H, Langendijk Johannes A, Vissink Arjan, Coppes Rob P
Department of Radiation Oncology, University Medical Center Groningen, The Netherlands.
Radiother Oncol. 2009 Feb;90(2):253-6. doi: 10.1016/j.radonc.2008.11.011. Epub 2009 Jan 10.
Administration of pilocarpine before irradiation can ameliorate radiation-induced hyposalivation. Indirect evidence suggests that this effect may be mediated through induction of a compensatory response. In this study, this hypothesis is tested directly, by assessing the proliferation of progenitor and secretory cells in irradiated and non-irradiated parotid gland tissue.
In a rat model, parotid glands were unilaterally irradiated with a single dose of 15 Gy, 60 min after administration of pilocarpine (4.0mg/kg). Rats were sacrificed for proliferating cell nuclear antigen (PCNA) labelling, assessing the number of proliferating progenitor and secretory cells, before, and 10h, 1, 3, 7, 10, 20 and 30 days after irradiation.
A small radiation-induced increase in PCNA expressing cells was observed, both in the acinar (secretory cells) and intercalated duct cell (containing the progenitor cells) compartment. This increment was significantly enhanced in pilocarpine pre-treated glands. In fact, in this group of animals increased proliferation was observed both in the irradiated and the shielded gland.
Amelioration of early loss of rat salivary gland function after radiation by pilocarpine pre-treatment is, at least in part, due to compensatory mechanisms through increased proliferation of undamaged cells.
照射前给予毛果芸香碱可改善辐射诱导的唾液分泌减少。间接证据表明，这种效应可能是通过诱导一种代偿反应介导的。在本研究中，通过评估照射和未照射的腮腺组织中祖细胞和分泌细胞的增殖情况，直接对这一假设进行了检验。
在大鼠模型中，在给予毛果芸香碱（4.0mg/kg）60分钟后，对一侧腮腺进行单次15Gy照射。在照射前以及照射后10小时、1天、3天、7天、10天、20天和30天，处死大鼠进行增殖细胞核抗原（PCNA）标记，评估增殖的祖细胞和分泌细胞数量。
在腺泡（分泌细胞）和闰管细胞（包含祖细胞）区室中，均观察到辐射诱导的PCNA表达细胞略有增加。在毛果芸香碱预处理的腺体中，这种增加显著增强。事实上，在这组动物中，照射侧和未照射侧腺体均观察到增殖增加。
毛果芸香碱预处理可改善大鼠辐射后唾液腺功能的早期丧失，至少部分是由于未受损细胞增殖增加的代偿机制所致。
