文章：

甲氨蝶呤化疗导致生长障碍、维生素D缺乏、骨量流失及肠道代谢改变——补充骨化三醇的效果研究

Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation

原文发布日期：1 September 2023

DOI: 10.3390/cancers15174367

类型: Article

开放获取: 是

英文摘要：

Vitamin D deficiency or insufficiency is prevalent in childhood cancer patients and survivors after chemotherapy; further studies are needed to investigate the underlying aetiology and effectiveness of vitamin D supplementation in preventing chemotherapy-induced bone loss. This study used a rat model of treatment with antimetabolite methotrexate to investigate whether methotrexate chemotherapy causes vitamin D deficiency and if vitamin D supplementation attenuates the resultant bone loss. Methotrexate treatment (five daily injections) decreased serum vitamin D levels (from 52 to <30 ng/mL), reduced body and bone lengthening and tibial trabecular bone volume, and altered intestinal vitamin D metabolism, which was associated with intestinal mucosal damage known to cause malabsorption of nutrients, including dietary vitamin D and calcium. During the early stage after chemotherapy, mRNA expression increased for vitamin D activation enzyme CYP27B1 and for calcium-binding protein TRPV6 in the intestine. During the intestinal healing stage, expression of vitamin D catabolism enzyme CYP24 increased, and that of TRPV6 was normalised. Furthermore, subcutaneous calcitriol supplementation diminished methotrexate-induced bone loss due to its effect suppressing methotrexate-induced increased bone resorption. Thus, in young rats, methotrexate chemotherapy causes vitamin D deficiency, growth impairments, bone loss, and altered intestinal vitamin D metabolism, which are associated with intestinal damage, and vitamin D supplementation inhibits methotrexate-induced bone loss.

摘要翻译： 

维生素D缺乏或不足在儿童癌症患者及化疗后幸存者中普遍存在；需进一步研究探讨其潜在病因及补充维生素D在预防化疗所致骨丢失中的有效性。本研究采用抗代谢药物甲氨蝶呤治疗的大鼠模型，探究甲氨蝶呤化疗是否会导致维生素D缺乏，以及补充维生素D能否减轻由此引发的骨丢失。甲氨蝶呤治疗（连续五日注射）降低了血清维生素D水平（从52 ng/mL降至<30 ng/mL），抑制了身体与骨骼纵向生长，减少了胫骨小梁骨体积，并改变了肠道维生素D代谢——这与已知会导致膳食维生素D及钙等营养素吸收不良的肠黏膜损伤相关。化疗后早期阶段，肠道中维生素D活化酶CYP27B1与钙结合蛋白TRPV6的mRNA表达增加；在肠道修复阶段，维生素D分解代谢酶CYP24表达上升，TRPV6表达恢复正常。此外，皮下补充骨化三醇通过抑制甲氨蝶呤诱导的骨吸收增强，减轻了甲氨蝶呤引发的骨丢失。因此，在幼年大鼠中，甲氨蝶呤化疗会导致维生素D缺乏、生长障碍、骨丢失及肠道维生素D代谢改变，这些变化与肠道损伤相关，而补充维生素D可抑制甲氨蝶呤诱导的骨丢失。

原文链接：

Methotrexate Chemotherapy Causes Growth Impairments, Vitamin D Deficiency, Bone Loss, and Altered Intestinal Metabolism—Effects of Calcitriol Supplementation