Freeman-Narrod M, Narrod S A, Custer R P
J Natl Cancer Inst. 1977 Sep;59(3):1013-7. doi: 10.1093/jnci/59.3.1013.
Methotrexate (MTX) inhibits the enzyme dihydrofolate reductase, which in turn limits the body's ability to perform transmethylation reactions. This study examined the hypothesis that the consequent deficiency of an important methylated compound, choline, may have contributed to the MTX-induced fatty change in the liver of W rats. Groups of rats were given MTX alone or MTX plus choline in varying dose combinations. All groups but one receiving the combined treatment showed a significantly lower triglyceride concentration in their livers and much less visible hepatocytic fat on histologic examination than did those given MTX alone. The protective effect of choline on the liver was dose related, the unaffected group having received a very small amount. Growth rate, survival, and hematopoietic depression due to MTX were unaltered by choline administration.
甲氨蝶呤（MTX）可抑制二氢叶酸还原酶，进而限制机体进行转甲基反应的能力。本研究检验了这样一个假设，即重要的甲基化化合物胆碱的缺乏可能导致了MTX诱导的W大鼠肝脏脂肪变性。将大鼠分组，分别给予单独的MTX或MTX与胆碱的不同剂量组合。除一组接受联合治疗外，所有接受联合治疗的组肝脏中的甘油三酯浓度均显著低于单独给予MTX的组，并且在组织学检查中可见的肝细胞脂肪也少得多。胆碱对肝脏的保护作用与剂量相关，未受影响的组接受的胆碱量非常少。给予胆碱不会改变MTX所致的生长速率、生存率和造血抑制。
