Coppes R P, Zeilstra L J, Vissink A, Konings A W
Department of Radiobiology, University of Groningen, The Netherlands.
Radiat Res. 1997 Sep;148(3):240-7.
To investigate whether secretory granules play a role in the radiosensitivity of the salivary glands of rats, parotid acinar cells, submandibular acinar cells and/or submandibular granular convoluted tubule (GCT) cells were degranulated prior to irradiation. Degranulation of GCT cells was obtained by pretreatment with phenylephrine (5 mg/kg, t = -60 min) and methacholine (3.75 mg/kg, t = -120 min). Degranulation of acinar cells was attained by pretreatment with isoproterenol (5 mg/kg, t = -90 min). Combinations of pretreatments were also tested. Irradiation was performed with a single dose of 15 Gy of X rays. Samples of parotid and submandibular/sublingual saliva were collected 4 days prior to and 1, 3, 6, 10 and 30 days after irradiation. Pretreatment with phenylephrine, isoproterenol and methacholine plus phenylephrine resulted in less radiation damage to parotid gland function as indicated by the lag phase and flow rate. Since the pretreatment with phenylephrine and phenylephrine plus methacholine did not degranulate parotid gland acinar cells, the observed protective effect on this gland cannot be explained by the "degranulation concept." Furthermore, salivary gland function was significantly greater 3 days after irradiation as a result of pretreatment with phenylephrine and phenylephrine plus methacholine compared to rats given only radiation. This may indicate recovery from damage rather than a reduced amount of initial damage. The sparing was most obvious for the later effects (6-30 days). Submandibular/sublingual gland function was improved significantly after pretreatment with methacholine plus phenylephrine, although no increase in degranulation of GCT cells was observed compared to pretreatment with phenylephrine alone, again not favoring the degranulation concept. The results indicate that the secretory granules do not play the often-assumed important role in the radiosensitivity of the salivary gland. The mechanism underlying the observed improvement of salivary gland function may involve second messenger-induced increases in proliferation of salivary gland cells resulting in recovery of tissue after the irradiation.
为研究分泌颗粒是否在大鼠唾液腺的放射敏感性中发挥作用，在照射前使腮腺腺泡细胞、下颌下腺腺泡细胞和/或下颌下颗粒曲管（GCT）细胞脱颗粒。通过用去氧肾上腺素（5mg/kg，时间t = -60分钟）和乙酰甲胆碱（3.75mg/kg，时间t = -120分钟）进行预处理来实现GCT细胞的脱颗粒。通过用异丙肾上腺素（5mg/kg，时间t = -90分钟）进行预处理来实现腺泡细胞的脱颗粒。还测试了预处理的组合。用15Gy的单次X射线剂量进行照射。在照射前4天以及照射后1、3、6、10和30天收集腮腺和下颌下腺/舌下腺的唾液样本。去氧肾上腺素、异丙肾上腺素以及乙酰甲胆碱加去氧肾上腺素的预处理导致腮腺功能的辐射损伤减轻，这通过延迟期和流速得以体现。由于去氧肾上腺素以及去氧肾上腺素加乙酰甲胆碱的预处理并未使腮腺腺泡细胞脱颗粒，因此观察到的对该腺体的保护作用无法用“脱颗粒概念”来解释。此外，与仅接受辐射的大鼠相比，由于去氧肾上腺素以及去氧肾上腺素加乙酰甲胆碱的预处理，照射后3天唾液腺功能显著更强。这可能表明是从损伤中恢复而非初始损伤量减少。这种保护作用在后期效应（6 - 30天）最为明显。乙酰甲胆碱加去氧肾上腺素预处理后，下颌下腺/舌下腺功能显著改善，尽管与单独用去氧肾上腺素预处理相比，未观察到GCT细胞脱颗粒增加，这同样不支持脱颗粒概念。结果表明，分泌颗粒在唾液腺的放射敏感性中并不发挥通常所认为的重要作用。观察到的唾液腺功能改善的潜在机制可能涉及第二信使诱导的唾液腺细胞增殖增加，从而导致照射后组织恢复。
