Protective Effect of Amifostine on High-Dose Methotrexate-Induced Small Intestinal Mucositis in Mice
Protective Effect of Amifostine on High-Dose Methotrexate-Induced Small Intestinal Mucositis in Mice
复制标题
氨磷汀对大剂量甲氨蝶呤所致小鼠小肠粘膜炎的保护作用
DOI：
10.1007/s10620-013-2826-3
复制
发表时间：
2013-11-01
影响因子：
3.1
通讯作者：
Hao, Li
中科院分区：
文献类型：
--
作者：
Chen, Changying;Tian, Li;Hao, Li
研究背景氨磷汀对放射性口腔黏膜炎有一定的保护作用，但对大剂量甲氨蝶呤引起的小肠黏膜损伤是否有保护作用尚不清楚，目的探讨氨磷汀对大剂量甲氨蝶呤引起的小肠黏膜炎的保护作用及其机制。高剂量甲氨蝶呤（HDMTX）组：单次高剂量甲氨蝶呤治疗;亚叶酸钙（CF）组：高剂量甲氨蝶呤治疗后CF治疗;氨磷汀组：氨磷汀治疗后高剂量甲氨蝶呤治疗;氨磷汀-CF组：氨磷汀治疗前高剂量甲氨蝶呤治疗后CF治疗。记录小鼠体重、绒毛高度和隐窝深度、粪便稠度、白色血细胞计数、死亡和存活。Bax和Bcl-2 mRNA的表达定量通过半定量PCR.ResultsCompared与HDMTX，CF，和氨磷汀治疗的小鼠相比，与氨磷汀-CF组治疗的小鼠更重，有更大的绒毛高度，隐窝深度，和正常的白色血细胞计数和更低的腹泻率和死亡率比HDMTX，CF和氨磷汀组。与HDMTX和CF groups.ConclusionsThe effect of amifostine plus CF is greater than amifostine or CF alone in preventing high-dose methodiazate-induced intestinal mucositis and improving intestinal recovery in mice相比，amifostine-CF小鼠肠上皮细胞凋亡显著减少。
BackgroundAmifostine has been shown to be capable of minimizing radiotherapy-induced oral mucositis, but whether it protects small intestinal mucosae from high-dose methotrexate-induced damage is presently unknown.AimWe aimed to evaluate the protective effect of amifostine against high-dose methotrexate-induced small intestinal mucositis and its mechanism.MethodsNinety Kunming mice were randomly divided into five experimental groups: saline control; high-dose methotrexate (HDMTX) group: treated with a single high dose of methotrexate; calcium folinate (CF) group: treated with high-dose methotrexate followed with CF; Amifostine group: treated with amifostine, followed with high-dose methotrexate; and amifostine-CF group: treated with amifostine pre-high-dose methotrexate and followed by CF post-high-dose methotrexate. Mouse weight, villus height and crypt depth, stool consistency, white blood cell count, death and survival were recorded. Bax and Bcl-2 mRNA expression were quantified by semi-quantitative PCR.ResultsCompared to the mice treated with HDMTX, CF, and amifostine, mice treated with Amifostine-CF group were heavier and had greater villus height, crypt depth, and normal white blood cell count and lower diarrhea rate and mortality than the HDMTX, CF and amifostine groups. There was a significant decrease in enterocyte apoptosis in amifostine-CF mice compared with the HDMTX and CF groups.ConclusionsThe effect of amifostine plus CF was greater than amifostine or CF alone in preventing high-dose methotrexate-induced intestinal mucositis and improving intestinal recovery in mice.