Vujaskovic Zeljko, Thrasher Bradley A, Jackson Isabel L, Brizel Marla B, Brizel David M
Department of Radiation Oncology, Duke University Medical Center, Durham, NC 27710, USA.
Int J Radiat Oncol Biol Phys. 2007 Oct 1;69(2):534-40. doi: 10.1016/j.ijrobp.2007.05.062.
This study was performed to evaluate the protective benefit of amifostine against esophageal injury from fractionated radiation in a rodent model.
Fractionated or sham esophageal irradiation was administered to Fisher-344 rats for 5 consecutive daily fractions of 9 Gy using 150 kV X-rays. Animals received an intraperitoneal injection of amifostine or placebo 30 min before each fraction. Histopathologic analyses for mucosal thickness, submucosal collagen deposition, activation of macrophages, oxidative stress and expression/activation of integrinalphavbeta6 and transforming growth factor (TGF)-beta were performed 5 days and 10 weeks after irradiation.
Pre-RT mean mucosal thickness was 35 microm in both the placebo and the amifostine groups. Five days post-RT, mean mucosal thicknesses were 30 microm in the placebo group versus 37 microm in the amifostine group (p = 0.024). At 10 weeks post-RT, the group receiving amifostine experienced a significant decrease in tunica muscularis damage (p = 0.002), submucosal collagen deposition (p = 0.027), and macrophage accumulation (p = 0.026) when compared with the placebo group. The levels of immunoreactivity for oxidative stress, TGF-beta, and integrinalphavbeta6 were significantly decreased 10 weeks post-RT in the group receiving amifostine treatment compared with placebo group.
This study demonstrates that amifostine given before each radiation fraction protects against acute and chronic esophageal injury in a rodent model. Protection of the mucosal epithelium integrity by amifostine prevents integrinalphavbeta6 expression which reduces TGF-beta activation and subsequent development of chronic esophageal injury in this model. Further investigation is necessary to determine the clinical relevance of these findings.
本研究旨在评估氨磷汀对啮齿动物模型中分次照射所致食管损伤的保护作用。
使用150 kV X射线对Fisher-344大鼠进行分次或假食管照射，连续5天，每天照射剂量为9 Gy。在每次照射前30分钟，动物接受腹腔注射氨磷汀或安慰剂。在照射后5天和10周进行组织病理学分析，评估黏膜厚度、黏膜下胶原沉积、巨噬细胞活化、氧化应激以及整合素αvβ6和转化生长因子（TGF）-β的表达/活化情况。
放疗前，安慰剂组和氨磷汀组的平均黏膜厚度均为35微米。放疗后5天，安慰剂组的平均黏膜厚度为30微米，而氨磷汀组为37微米（p = 0.024）。放疗后10周，与安慰剂组相比，接受氨磷汀治疗的组在肌层损伤（p = 0.002）、黏膜下胶原沉积（p = 0.027）和巨噬细胞聚集（p = 0.026）方面均有显著降低。与安慰剂组相比，接受氨磷汀治疗的组在放疗后10周时氧化应激、TGF-β和整合素αvβ6的免疫反应水平显著降低。
本研究表明，在每次放疗前给予氨磷汀可保护啮齿动物模型免受急性和慢性食管损伤。氨磷汀对黏膜上皮完整性的保护可防止整合素αvβ6的表达，从而减少TGF-β的活化以及该模型中慢性食管损伤的后续发展。有必要进一步研究以确定这些发现的临床相关性。
