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AIM: To observe the effects of rapamycin pregnancy intervention on cognitive function of autism model in rat offspring. METHODS: Fourteen pregnant rats were randomly divided into normal group (n = 3), model group (n = 4), rapamycin (RAPA) control group (n =3) and intervention group (n = 4). The model group and intervention group were i.p. injected with sodium valproate 600 mg/kg at embryonic day (E) 12.5 to establish autism model in rat offspring. RAPA control group and intervention group were i.g. given RAPA 4 mg/kg every day from the 13th day of gestation until the offspring rats were weaned at 23 days. After the birth of the above four groups of pregnant rats, 15, 27, 21 and 26 offspring male rats were selected to conduct behavioral tests to identify the model. Then, paw withdrawal mechanical threshold (PWMT), tail flick latency (TFL) evoked under different light intensity and learning and memory function of offspring rats were further detected. RESULTS: Rat offspring in the model group had lower growth and development indexes and exploratory behavior ability, but stronger repetitive stereotyped behavior compared with the normal group (P < 0.05), while the indexes between the intervention group and model group were reversed (P < 0.05). The model group had higher PWMT than normal group (P < 0.01) and the PWMT of intervention group was lower than that of model group (P < 0.01). The TFLs of rats in 4 groups showed a timed dose-response relationship (TDRR, P < 0.01), that is, TFLs were shortened with the increase of light intensity. The TDRR curve of model group shifted to right compared with normal group (P < 0.01) and intervention group shifted to left compared with model group (P < 0.01). At the light intensity of Focus 34, 51 and 76, the TFLs of model group were longer than those of normal group (P < 0.01) and intervention group had shorter TFLs compared with model group (P<0.01). In spatial probing trial of Morris water maze test, the platform crossover number in model group was less than that in normal group (P<0.01) and that in intervention group was more than model group (P < 0.05). CONCLUSION: RAPA intervention during pregnancy may alleviate behavior disorder, pain tolerance and memory function of autism model in rat offspring to some extent.
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Aim To establish the pharmacokinetic-pharmacodynamic(PK-PD) modeling to characterize the antipyretic effects of coptisine, an active component in coptis chinensis on rats.Methods Nine healthy male Sprague-Dawley(SD) rats were randomly divided into three groups, each with three.The rats in the first group were injected intravenously with lipopolysaccharide(LPS,100 μg·kg-1) alone.The second and third group rats were given coptisine high-dose(3.87 mg·kg-1) and coptisine low-dose(1.93 mg·kg-1) by tail vein injection at 30 min after LPS injection, respectively.Body temperature was measured at different time points, and blood samples from tail vein were collected simultaneously.The blood concentration of coptisine was determined by ultra performance liquid chromatography.Monolix software was used to model PK-PD of coptisine mean plasma concentration and temperature effects,by population computation with non-covariates.Besides.the model with advantage was selected by the fitting goodness.Results Coptisine could inhibit body temperature of endotoxin-induced fever in rats significantly.Two-compartment linear elimination model was used to describe the final PK model.Gaussian function, an input function of body temperature changes, which was used to depict PD model, the PK and PD models were connected by the Emax model.At last, the final model was fitted better;the fitting results indicated that the EC50 of antipyretic effect of coptisine was 89.7 μg·L-1, and the Emax was 1.88℃.Conclusions Coptisine has a powerful anti-pyretic effect on endotoxin-induced pyrexia of rats with high potency, Low in vivo distribution and quick clearance.