国产^(13)C-美沙西丁呼气试验对小鼠急性肝损伤的评价

Evaluation of mouse acute liver damage by breath test with domestically synthesized ^(13)C-methacetin

目的建立一套简单易操作并在小鼠活体上进行的^(13)C呼气试验检测系统,并探讨国产^(13)C-美沙西丁呼气试验(^(13)C-MBT)对小鼠急性肝损伤的诊断价值。方法^(13)C-美沙西丁经扑热息痛甲烷化合成标记。采用四氯化碳(CCl_4)腹腔注射制作小鼠急性肝损伤模型,造模后饲养1个月复制小鼠急性肝损伤恢复模型,行肝脏病理组织学检查和肝功能血液生化学指标检测,于多个时间点采集活体小鼠^(13)C-美沙西丁灌胃后呼出的气体,以红外线能谱仪(IRIS)检测并绘制呼气峰值(DOB)曲线。结果正常对照组小鼠于灌胃给药后6～8 min时呼气^(13)C达到峰值(51.9±2.04),随后缓慢下降至本底值;模型组于灌胃给药后16 min左右达到峰值(26.37±5.74),随后亦缓慢下降至本底值,两组间差异有统计学意义(P<0.05)。当急性肝损伤恢复模型组和对照组小鼠在相同条件下饲养1个月后,重复^(13)C-美沙西丁呼气检测后两组DOB峰值及达峰时间差异无统计学意义(P>0.05)。结论^(13)C-MBT可在小鼠活体状态下准确、方便地采集和检测呼出气体的^(13)CO_2变化,并正确评估其肝功能的损伤和恢复情况。

Objective To establish a convenient ^13C-breath test system in live mice, and investigate the value of ^13C- methacetin breath test （^13 C-MBT） in the diagnosis of acute liver damage of mice with domestically synthesized ^13C- methacetin. Methods Domestically synthesized ^13C-methacetin was prepared from acamol by methylation. Abdominal injection of CCl4 was adopted to duplicate acute liver damage of mice, then the mice were housed under normal laboratory condition for a whole month to gain recovery, which were indentified by hepatic pathological examinations and biochemical tests of liver function. After fasting, the mice were orally administered ^13C-methacetin, and the expired air was collected at various time points. Infrared spectrometer was employed, and delta over baseline （DOB） curves of ^13C-exhalation were drawn. Results Six to eight min after administration of ^13C-methacetin, the rate of ^13C-exhalation peaked in controlgroup （51. 9 ± 2. 04）, and decreased thereafter. Sixteen min after administration of ^13C-methacetin, the rate of ^13C- exhalation peaked in model group （26.37 ± 5.74）, and decreased thereafter. There were significant differences between these two groups （P 〈 0.05）. There was no significant difference in peak value and time to reach the peak on DOB curves of ^13C-methacetin breath test after the two groups of mice were housed under the same condition for a month （P 〉 0.05）. Conclusion ^13C-MBT facilitates the collection and evaluation of ^13CO2 in the expired air of live mice, and yields precise reflection of alterations of liver function in acute liver injury and functional recovery.