| Objective:To evaluate the clinical effect of Fuguiyizhi decoction in the treatment of children with Autism Spectrum Disorder(ASD)with yang deficiency in the spleen and kidney syndrome.To establish a Valproic Acid(VPA)-induced ASD rat model and evaluate its face validity,and to evaluate the behavioral changes of rats before and after treatment with Fuguiyizhi decoction,so as to lay the foundation for future research.Methods:(1)Clinical trial methods:Sixteen ASD children with yang deficiency in the spleen and kidney syndrome were enrolled from the Third Affiliated Hospital of Beijing University of Chinese Medicine.The patients were treated with oral Fuguiyizhi decoction,twice a day,for 12 weeks.Autism Child Behavior Checklist(ABC),Autism Treatment Rating Scale(ATEC)and self-designed TCM syndrome scale were used to score the scores before and after treatment.SPSS20.0 was used for statistical analysis,and the clinical efficacy of Fuguiyizhi decoction in the treatment of ASD children with yang deficiency in the spleen and kidney was evaluated by comparing the changes of scores before and after treatment.(2)According to Schneider’s modeling method,female Sprague-Dawley rats were intraperitoneally injected with 500 mg/kg VPA on day 12.5 of gestation to establish the ASD rat model.The body weight of the rats was measured on the 7th(P7),14th(P14),21st(P21)and 28th(P28)days after birth.Eye opening was measured from P12 to P15.The directional orientation ability of rats was tested at P7-P10.The swimming ability of rats was detected at P9,P11,P13 and P15.Three box social behavior test,open field test and self-care behavior test were performed from P28 to P30 to evaluate the face validity of the VPA-induced ASD rat model.The rats were randomly divided into blank group(n=5),model group(n=5),low-dose group(n=5),medium-dose group(n=5)and high-dose group(n=4).The ASD model rats were treated with different concentrations of Fuguiyizhi decoction granule.The rats in the highdose group were given high-dose Fuguiyizhi decoction solution(2.15 g/ml),those in the medium-dose group were given medium-dose Fuguiyizhi decoction solution(1.07 g/ml),and those in the low-dose group were given low-dose Fuguiyizhi decoction solution(0.52 g/ml).The blank group and the model group were given the same amount of pure water for 28 days.After the end of gavage treatment,the rats were tested for three-box social behavior test,open field test and self-care behavior test again.SPSS20.0 was used for statistical analysis,and the differences in behavioral scores before and after treatment and among the groups were compared to evaluate the therapeutic effect of Fuguiyizhi decoction on the behavior of ASD model rats.Results:(1)Clinical trial results:Of the 16 patients,15 were male and 1 was female,with an average age of 7.18±2.74 years,and the youngest was 2 years old and the oldest was 14 years old.The total score of ABC after treatment was significantly lower than that before treatment,and the difference was statistically significant(P<0.001),among which the sensory ability score decreased the most significantly(P<0.001).The total score of ATEC after treatment was significantly lower than that before treatment(P<0.001),and the differences in social ability score and health physiological behavior score were statistically significant(P<0.001).After treatment,the scores of the self-made TCM syndrome scale were lower than those before treatment,and the difference was statistically significant(P<0.001).Among them,the scores of communication disorder in the main symptom part decreased most significantly(P<0.001),and the scores of facial expression,movement and appetite in the secondary symptom part decreased most significantly(P<0.001).In terms of safety,there were no abnormalities in blood and urine routine,liver and kidney function tests before and after treatment,and the patients denied adverse reactions during treatment.(2)The results of animal experiment:in the control group,the fertility rate of pregnant mice was 100%,and the survival rate of offspring mice was 100%.In the ASD model group,the maternal fertility rate was 33.33%,and the survival rate of offspring was 69.05%.At P7,P14,P21,and P28,the body weight of offspring mice in the ASD model group was lower than that in the blank control group,and the difference was statistically significant(P<0.05).At P14 and P15,the ASD model group had a significantly lower rate of eye opening than the control group(P<0.05).On P7,the offspring rats in the ASD model group had a significantly lower directional orientation ability than those in the control group(P<0.01).The swimming ability test showed that at P9,the offspring rats in the ASD model group had a significantly lower directional orientation ability than those in the control group(P<0.05).In the threebox social behavior test before treatment,the blank group had significantly higher social ability index and social preference index than the other four groups(P<0.001),and there was no significant difference among the other four groups(P>0.05).In the open field test,the blank group had a significantly lower proportion of time in the central area than the other four groups(P<0.001),and there was no significant difference among the other four groups(P>0.05).In the self-care behavior test,there was no significant difference in the frequency of self-care among the five groups before treatment(P>0.05).In the three-box social behavior test,the social ability index and social preference index of the blank group were higher than those of the other four groups,and the differences were statistically significant(P<0.001).The social ability index and social preference index of the high-dose group were higher than those of the model group,low-dose group and medium-dose group,and the differences were statistically significant(P<0.05).There was no significant difference among the other three groups(P>0.05).In the open field test,the blank group had a significantly lower proportion of time in the central area than the other four groups(P<0.001),and there was no significant difference among the other four groups(P>0.05).In the self-care behavior test,there was no significant difference in the frequency of self-care among the five groups after treatment(P>0.05).Compared before and after treatment,the social ability index and social preference index of the high-dose group were improved,and the difference was statistically significant(P<0.05).The time ratio of central area in open field test decreased,but the difference was not statistically significant(P>0.05).There was no significant difference in the frequency of self-care(P>0.05).There was no significant difference in the behavioral indexes before and after treatment in the other four groups(P>0.05).Conclusions:Fuguiyizhi Decoction can improve the core symptoms of ASD such as social disorder and repetitive stereotypical behaviors to varying degrees by warming Yang and opening the orifics and supplementing essence and filling marrow.It also has significant improvement and therapeutic effect on appetite,physical movement ability,enuresis and other accompanying symptoms of children with ASD.Fuguiyizhi decoction is safe and has no adverse reactions in the treatment of ASD.The animal experiment showed that the VPAinduced ASD rat model had good face validity.After 1 month of treatment with high-dose Fuguiyizhi decoction,the social behavior ability of ASD model rats was improved,and the anxiety-like emotions also tended to be improved.It is further confirmed that Fuguiyizhi decoction has a therapeutic effect on the social dysfunction of ASD,and its specific mechanism needs to be further explored. |
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