动物实验,核磁共振（NMR） z-bo 2020-08-22 470

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

　　Method: Twenty-four healthy male Wistar rats were randomly divided into four groups: carbamazepine high, medium and low dose groups and normal control group, each with 6 rats. After 7 days of continuous gastric administration, blood was collected from the abdominal aorta after anesthesia, the serum drug concentration was measured by high performance liquid chromatography, the serum 1HMR spectrum was measured by nuclear magnetic resonance technology, pattern recognition analysis was performed, and the pathology was determined. Take liver and kidney tissues for histological examination.

　　Results: The stable plasma concentrations of carbamazepine in the high, medium and low dose groups were 14.64±1.41, 8.54±1.19 and 4.56±0.64μg, respectively? The liver in the ml-1, high-dose carbamazepine group was slightly swollen. There were no obvious lesions in kidney tissues in each group. Lower serum propylene diamine, deoxycorticosterone, dehydrocholesterol, betaine, β-alanine, cystathionine, 4-methyl-2-pentanoic acid and creatine, sugar, lactic acid, succinic acid, acetyl phosphate, The content of adipic acid levels has increased. PCA principal component analysis showed that the treatment and control metabolites were significantly different. There is no significant difference in the metabolic profile between different doses of carbamazepine, just the level of metabolites.

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