Experimental Studies On Evaluation Of Hepatic Function By ～(13)C-methacetin Breath Test In Rats With Carbon Tetrachloride-induced Acute Liver Injury

Objective: To investigate the characteristics of 13C- methacetin breath test(13C-MBT) as a tool to monitor hepatic function of rats with acute liver injury induced by carbon tetrachloride(CCl4), and the relations between these results with those of hepatic pathological changes and biochemical tests of the liver function.Methods: Abdominal injection of CCl4 was adopted to duplicate rats acute liver injury model. Thirty-two healthy female Wistar rats, weighing 180～220g, were randomly divided into four groups, normal control group, acute liver injury groups of 24h, 48h and 72h after injection of CCl4. Infrared isotope spectrometry (IRIS) was used to design the detect program and the method of rats 13C-MBT . And after 13C- methacetin administered by gavage, thirty-one breath samples were taken and measured every two minutes within 60 minutes. The changes of the three parameters of the duration to peak (T) of 13CO2 DOB (delta over baseline) curve, 13CO2 maximum metabolisation Velocity (MVmax) and 13CO2 cumulative dose within 60 minutes (CUM60) were determined. The hepatic pathological changes and biochemical tests of the liver function were also determined. Moreover, correlation between the parameters of 13C-MBT and these indexes of hepatic pathological changes and biochemical tests were analyzed. The expression of cytochrome P450 1A2 (CYP1A2) in liver tissues was observed by immunohistochemistry technique.Results: The parameter of 13C-MBT T significantly discriminated between controls (24.50±4.50min) and acute liver injury rats of 24h (41.50±2.98min),48h (41.75±2.92min),72h(30.25±5.18min)after injection of CCl4 (F=36.36,p<0.001). MVmax existed statistically significant differences between rats of control group (60.53±7.18%) and all acute liver injury groups (24h group 26.85±7.54% , 48h group 35.95±9.96%, 72h group 48.65±10.53%, F=21.76,p<0.001). The same results were obtained by compared CUM60 between four groups (control group 40.56±4.33%, 24h group 21.19±6.83% , 48h group 26.85±6.09%, 72h group 35.39±6.08%, F=17.14,p<0.001). The parameters of 13C-MBT MVmax and CUM60 of acute liver injury rats were significantly correlated to liver index, hepatic pathological grades and serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL),γ-glutamyl transferase (GGT), total bile acid (TBA) (p all less than 0.01). The expression of CYP1A2 in rats liver tissues of acute liver injury was decreased under the observation by light...