Effects of Guipi Pill on behavior and brain 5-HT content in rats with autism spectrum disorder modeled by fecal microbiota transplantation
Objective To verify the efficacy of Guipi Pill in alleviating core symptoms in offspring rats with autism spectrum disorder(ASD),to observe its effects on the content of 5-hydroxytryptamine(5-HT)in the brain,and to explore the correlation between its efficacy and the level of 5-HT in the brain.Methods Ten SPF SD pregnant rats were randomized into normal pregnant group(n=3)and fecal microbiota transplantation(FMT)pregnant group(n=7).The FMT pregnant group was modeled by FMT method.On the 28th day of birth,30 male rats were screened by behavioral test to meet the ASD disease model.Then they were randomly subdivided into model group(an equal volume of normal saline),the low-,medium-,and high-dose(0.75 g/kg,1.5 g/kg,3 g/kg)Guipi Pill groups,and the Bifidobacterium(0.5 g/kg)group,with six rats in each group.In addition,six normal male rats were set as normal group(an equal volume of normal saline).Each group was given intragastric administration for 14 d,once a day.The body weight of rats was recorded,the efficacy was evaluated by behavioral test,the content of 5-HT in the forehead of rats was determined by ELISA,and the correlation between sociability,social novelty and 5-HT in offspring rats was analyzed by rank correlation analysis.Results Compared with the normal pregnant group,the offspring rats in the FMT pregnant group showed longer eye opening time(P<0.05)and lower body weight(P<0.05).Before treatment,compared with the normal group,the model group showed lower sociability(P<0.05)and social novelty(P<0.05)but higher degree of anxiety(P<0.05).After two weeks of medication,compared with the normal group,the model group showed lower sociability(P<0.05),lower social novelty(P<0.05),higher degree of anxiety(P<0.05),and lower body weight and 5-HT content(P<0.05).Compared with the model group,each treatment group showed higher sociability(P<0.05),higher social novelty(P<0.05),lower degree of anxiety(P<0.05),and higher 5-HT content(P<0.05).The body weight of the medium-and high-dose Guipi Pill groups and the Bifidobacterium group increased(P<0.05).Compared with the high-dose Guipi Pill group,the low-dose Guipi Pill group had lower sociability(P<0.05),lower social novelty(P<0.05),and lower body weight and content 5-HT(P<0.05),meanwhile,the medium-dose Guipi Pill group had lower 5-HT content(P<0.05)and the Bifidobacterium group had lower social novelty(P<0.05).Correlation analysis showed that the social preference coefficient and novelty preference coefficient of ASD rats were significantly and positively correlated with 5-HT content(P<0.05).Conclusion Guipi Pill can significantly alleviate ASD-like behavior in FMT offspring rats,and its mechanism may be related to the up-regulation of 5-HT content in the brain.