Study of Jiawei Xiehuangsan regulating Glu/GABA-Gin metabolic circuit in treatment of children with tic disorder
Objective To study the regulatory mechanism of Jiawei Xiehuangsan on Glu/GABA-Gln metabolic circuit in the striatum of tic disorder rats.Methods 40 SPF-grade SD rats were divided into blank group(n=10)and modeling group(n=30)by random number table method,establishing a model using IDPN intraperitoneal injection induction method.The stereotype behavior score of rats≥2 indicates successful modeling.The model rats were randomly and evenly divided into a model group,a tiapride group,and a Jiawei Xiehuangsan group,and orally administered for 4 weeks.Jiawei Xiehuangsan group was given concentrated decoction of Jiawei Xiehuang-san,tiapride group was given tiapride suspension,blank group and model group were given normal saline,all of which were given 10ml/kg,once a day.After successful modeling,conduct weekly rat behavioral evaluations.The striatum of rats were collected 24 hours after administration,and pathological changes were observed by HE staining.The mRNA and protein expressions of GAD,GS and GABAAR were detected by real-time PCR and western blot,respectively.The content of Glu and GABA was determined by ELISA.Results Com-pared with the blank group,the motor behavior,stereotype behavior,categorical stereotype behavior and open shelter experiment score of rats in the modeling group was increased(P＜0.01).HE staining in the striatum of model group showed neuronal degeneration and nec-rosis and glial cell proliferation.The pathological changes of striatum in tiapride group and Jiawei Xiehuangsan group were reduced,and the Jiawei Xiehuangsan group was the lightest.After 4 weeks of treatment,the motor behavior,stereotype behavior,categorical stereotype behavior and open shelter experiment scores of tiapride group and Jiawei Xiehuangsan group decreased(P＜0.01).Compared with blank group,there was no significant difference in Glu content in striatum of model group(P＞0.05),GABA content decreased(P＜0.05),mRNA and protein expressions of GS were increased(P＜0.05),and relative mRNA and protein expressions of GAD and GABAAR were decreased(P＜0.05).Compared with model group,the mRNA expressions of GS in tiapride and Jiawei Xiehuangsan groups were de-creased(P＜0.05,P＜0.01),and the mRNA expressions of GAD and GABAAR were increased in both groups(P＜0.01).Com-pared with model group,the expression of GS protein in tiapride group and Jiawei Xiehuangsan group was decreased(P＜0.05),while the expression of GAD and GABAAR protein was increased(P＜0.01).Compared with model group,Glu content in tiapride group had no significant change(P＞0.05),Glu content in Jiawei Xiehuangsan group was decreased(P＜0.01),and GABA content in both groups was increased(P＜0.05).Conclusion Jiawei Xiehuangsan can improve the behavioral score of tic rats,protect striatal neurons,improve glial cell proliferation,and exert anti-tic effect,which may be related to regulating the Glu/GABA-GLN metabolic circuit,improving the imbalance of striatal amino acid neurotransmitters,and regulating the neural excitation/inhibition ratio.
Tic disorderJiawei XiehuangsanGlu/GABA-Gln metabolic circuitNeural E/I ratio
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