Zeilstra L J, Vissink A, Konings A W, Coppes R P
Department of Radiobiology, University of Groningen, The Netherlands.
Int J Radiat Biol. 2000 Mar;76(3):419-29. doi: 10.1080/095530000138763.
To understand early and late radiation-induced loss of function of the submandibular gland, changes in cell number were documented and correlated with data on gland function. Modulation of the radiation effect by sialogogues was used to investigate possible mechanisms of action.
Rats were irradiated with a single dose of 15 Gy of X-rays after pre-treatment with either saline, the muscarinic receptor agonists methacholine or pilocarpine, the adrenergic receptor agonist phenylephrine or methacholine plus phenylephrine. Before and 1-240 days after irradiation, submandibular saliva flow rate was measured. At the same time points and from comparable animals submandibular glands were carefully extirpated, weighed and prepared for light microscopic examination.
Soon after irradiation (<30 days) no significant loss of cells was observed, whereas the gland function was severely compromised. Sialogogue pre-treatment attenuated the radiation-induced loss of gland function. At later intervals a considerable loss of acinar cells and to a lesser extent loss of granular convoluted tubule cells were observed. Gland function subsequently declined slowly. Pre-treatment with sialogogues gave transient protection against cell loss and loss of gland function.
The lack of cell loss observed soon after irradiation indicates that the observed reduction in gland function was caused by a compromised functioning of the acini. The later loss of cells is probably due to death of cells that normally proliferate, leading to a further reduced secretory capacity. Protection of gland morphology and function by sialogogues at later times must therefore involve resistance of progenitor cells to radiation-induced cell death.
为了解早期和晚期辐射诱导的下颌下腺功能丧失情况，记录细胞数量的变化并将其与腺体功能数据相关联。使用促唾液分泌剂调节辐射效应，以研究可能的作用机制。
大鼠在预先用生理盐水、毒蕈碱受体激动剂乙酰甲胆碱或毛果芸香碱、肾上腺素能受体激动剂去氧肾上腺素或乙酰甲胆碱加去氧肾上腺素处理后，接受单次15 Gy的X射线照射。在照射前及照射后1 - 240天，测量下颌下腺唾液流速。在相同时间点，从可比动物身上小心摘除下颌下腺，称重并制备用于光镜检查。
照射后不久（<30天），未观察到细胞显著丢失，而腺体功能严重受损。促唾液分泌剂预处理减轻了辐射诱导的腺体功能丧失。在较晚时间段，观察到腺泡细胞大量丢失，颗粒曲管细胞丢失程度较轻。随后腺体功能缓慢下降。促唾液分泌剂预处理对细胞丢失和腺体功能丧失提供了短暂保护。
照射后不久未观察到细胞丢失，这表明观察到的腺体功能降低是由腺泡功能受损引起的。后期细胞丢失可能是由于正常增殖的细胞死亡，导致分泌能力进一步降低。因此，促唾液分泌剂在后期对腺体形态和功能的保护必须涉及祖细胞对辐射诱导的细胞死亡的抗性。
