动物造模 z-bio 2022-07-25 282

　　OBJECTIVE: To analyze the effect of carbamazepine on the serum metabolome of rats after intragastric administration using nuclear magnetic resonance (NMR)-based metabolomics technology.

　　Methods: Twenty-four healthy male Wistar rats were randomly divided into 4 groups: carbamazepine high-dose, medium-dose and low-dose groups and normal control group, with 6 rats in each group. After continuous intragastric administration for 7 days, blood was collected from the abdominal aorta after anesthesia, and serum drug concentrations were detected by high performance liquid chromatography. examine.

　　RESULTS: Steady-state plasma concentrations of carbamazepine in high, medium and low dose groups were 14.64±1.41, 8.54±1.19, 4.56±0.64 μg·ml-1, respectively. The liver in high dose carbamazepine group was slightly swollen. There were no obvious lesions in renal tissue in the group. Serum levels of propylenediamine, deoxycorticosterone, dehydrocholesterol, betaine, β-alanine, cystathionine, 4-methyl-2-pentanone acid, creatine decreased, carbohydrates, lactic acid, succinic acid Acid, acetylphosphoric acid, adipic acid content increased. PCA principal component analysis showed that the metabolites in the administration group and the control group were significantly different and could be distinguished. There was no significant difference in the metabolic profile between different dose groups of carbamazepine, only the content of metabolites was different.

　　Conclusion: Carbamazepine has a significant effect on the metabolic process of normal rats, which provides a basis for clinical drug monitoring and drug safety of carbamazepine. The use of NMR technology has unique advantages and important value in the evaluation of drug pharmacodynamics and toxicology.