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Single-Dose Radiation-Induced Oral Mucositis Mouse Model

机译:单剂量辐射诱导的口腔粘膜炎小鼠模型

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The generation of a self-resolved radiation-induced oral mucositis (RIOM) mouse model using the highest possibly tolerable single ionizing radiation (RT) dose was needed in order to study RIOM management solutions. We used 10-week-old male BALB/c mice with average weight of 23?g for model production. Mice were treated with an orthovoltage X-ray irradiator to induce the RIOM ulceration at the intermolar eminence of the animal tongue. General anesthesia was injected intraperitoneally for proper animal immobilization during the procedure. Ten days after irradiation, a single RT dose of 10, 15, 18, 20, and 25?Gy generated a RIOM ulcer at the intermolar eminence (posterior upper tongue surface) with mean ulcer floor (posterior epithelium) heights of 190, 150, 25, 10, and 10?μm, respectively, compared to 200?μm in non-irradiated animals. The mean RIOM ulcer size % of the total epithelialized upper surface of the animal tongue was RT dose dependent. At day 10, the ulcer size % was 2, 5, 27, and 31% for 15, 18, 20, and 25?Gy RT, respectively. The mean relative surface area of the total epithelialized upper surface of the tongue was RT dose dependent, since it was significantly decreased to 97, 95, 88, and 38% with 15, 18, 20, and 25?Gy doses, respectively, at day 10 after RT. Subcutaneous injection of 1?mL of 0.9% saline/6?h for 24?h yielded a 100% survival only with 18?Gy self-resolved RIOM, which had 5.6?±?0.3?days ulcer duration. In conclusion, we have generated a 100% survival self-resolved single-dose RIOM male mouse model with long enough duration for application in RIOM management research. Oral mucositis ulceration was radiation dose dependent. Sufficient hydration of animals after radiation exposure significantly improved their survival.
机译:为了研究RIOM管理解决方案,需要使用可能最高耐受的单电离辐射(RT)剂量生成自分辨辐射诱发的口腔粘膜炎(RIOM)小鼠模型。我们使用平均体重为23?g的10周大的雄性BALB / c小鼠进行模型制作。用正电压X射线辐照器治疗小鼠以在动物舌的磨牙间突出处诱导RIOM溃疡。在手术过程中腹膜内注射全身麻醉以适当固定动物。照射后十天,单次RT剂量10、15、18、20和25?Gy在磨牙间隆起(后舌上表面)产生RIOM溃疡,其平均溃疡基底(后上皮)高度为190、150,分别为25μm,10μm和10μm,而未辐照的动物为200μm。动物舌头总上皮化上表面的平均RIOM溃疡大小%与RT剂量有关。在第10天,15、18、20和25?Gy RT的溃疡大小%分别为2、5%,27%和31%。舌头上皮总上表面的平均相对表面积是RT剂量依赖性的,因为在15、18、20和25?Gy剂量下,舌头上皮化的上表面的平均相对表面积分别显着降低至97%,95%,88%和38%。 RT后的第10天。皮下注射1?mL的0.9%生理盐水/ 6?h持续24?h,仅用18?Gy自溶性RIOM(溃疡持续时间为5.6?±0.3?3天)才能获得100%的存活率。综上所述,我们已经产生了100%生存期自解决的单剂量RIOM雄性小鼠模型,其持续时间足够长,可用于RIOM管理研究。口腔粘膜炎溃疡是辐射剂量依赖性的。辐射照射后动物的充足水分可显着提高其存活率。

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