A study of 5-FU metabolism in fatty liver and hepatocellular carcinoma induced by choline deficient diet, using 19F-MRS.

使用 19F-MRS 研究缺乏胆碱饮食诱导的脂肪肝和肝细胞癌中 5-FU 代谢。

• 批准号: 08671034
• 负责人: NISIHTANI Hiromu
• 金额: $ 1.41万
• 依托单位: UNIVERSITY OF TOKUSHIMA
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671034/
• 关键词: 19F-MR spectroscopy; choline deficient diet; fatty liver; 5-fluorouracil; 19F-MR spectruscopy; 31P-MR spectruscopy

Purpose : To assess fatty liver by 19F-MRS and 31P-MRS,observing 5-fluorouracil metabolism (anabolize to fluoronucleotide (Fnct) and catabolize to alpha-fluoro-beta-alanine (FBAL)) and fructose metabolism (mainly inverted to fructose-1-phosphate), respectively.Materials and Methods : Male Wistar Slc rats were examined on BEM170/200 (4.7T,Otsuka Electronics) with 17mm-diameter surface coil. Fatty liver was induced by choline deficient diet (CD diet) given for 2 or 4 weeks. 19F-MR spectra were obtained for 100min.after 5-FU intravenous injection. 31P-MR spectra were obtained pre and post fructose injection. 19F-MRS and 31P-MRS studies were performed in separated experiments.Results : In 19F-MRS,high Fnct peak and suppressed FBAL peak was observed in CD diet group. In 31P-MRS,no significant difference could be seen between CD diet group and control diet group about the time course of phosphomonoester (PME) and adenosine-triphosphate (ATP).Conclusion : We detected the high peak of Fnct that may reflect the recovering reaction from liver damage but the difference of fructose metabolism was not evident. In damaged liver, the injured metabolic pathway and severity is different among the diseases and individuals. The dynamic study with in vivo MRS has the possibility to detect the impaired point and the severity. We proposed that it is very important to try some different methods to evaluate liver function and in vivo dynamic MRS may be valuable for it.

目的：材料和方法：雄性Wistar S1 c大鼠，采用BEM 170/200（4.7T，OtsukaElectronics）17 mm直径表面线圈，观察5-氟尿嘧啶代谢（合成为氟尿嘧啶（Fnct），分解为α-氟-β-丙氨酸（FBAL））和果糖代谢（主要转化为1-磷酸果糖），应用19 F-MRS和31 P-MRS评价脂肪肝。用胆碱缺乏饲料（CD饲料）诱导脂肪肝2或4周。静脉注射5-FU后100分钟获得19 F-MR谱。在果糖注射前后获得31 P-MR谱。结果：在19 F-MRS中，CD饮食组Fnct峰高，FBAL峰低; 31 P-MRS显示，CD饮食组和对照饮食组磷酸单酯（PME）和三磷酸腺苷（ATP）的时程无明显差异。结论：检测到Fnct的高峰，可能反映了肝脏损伤的恢复反应，但果糖代谢差异不明显。在肝脏损伤中，不同疾病和个体的代谢途径和损伤程度不同。在体MRS动态研究有可能发现损伤点和损伤程度。我们认为，尝试不同的方法来评估肝功能是非常重要的，活体动态MRS可能是有价值的。

项目成果

H.Otsuka,M.Harada: "In vivo 19F-MRS Observation of 5-Fluorouracil Metabolism in Fatty Liver Induced by Choline-Deficient Diet." Proceedings in ISMRM.4. 4・3. 1044 (1996)

H.Otsuka、M.Harada：“胆碱缺乏饮食诱导的脂肪肝中 19F-MRS 代谢的体内观察”，ISMRM.4·3 论文集。

大塚秀樹、原田雅史: "コリン欠乏食誘発脂肪肝における5-FU代謝のin vivo 19F-MRSによる観察" 日本磁気共鳴医学会雑誌. 16巻5号. 167-175 (1996)

Hideki Otsuka、Masashi Harada：“胆碱缺乏饮食诱导的脂肪肝中 5-FU 代谢的体内 19F-MRS 观察”日本医学磁共振学会杂志，第 16 卷，第 5 期。167-175 (1996)

H.Otsuka, M.Harada, et al: "Effects of hepatic impairment on the metabolism of fructose and 5-fluorouracil,as studied in fatty liver models,using in vivo 31P-MRS and 19F-MRS." Magn Reson Imag. (現在印刷中).

H.Otsuka、M.Harada 等人：“使用体内 31P-MRS 和 19F-MRS 在脂肪肝模型中研究肝损伤对果糖和 5-氟尿嘧啶代谢的影响。” （目前正在印刷中）。

Hideki Otsuka: "Effects of hepatic impairment on the metabolism of fructose and 5-fluorouracil, as studied in fatty liver models using in vivo 31P-MRS and 19F-MRS." Magn.Reson.Imag.(Now Printing).

Hideki Otsuka：“使用体内 31P-MRS 和 19F-MRS 在脂肪肝模型中研究了肝损伤对果糖和 5-氟尿嘧啶代谢的影响。”