Experimental Study on the Intervention of Qiangzhi Formula in Tic Disorder by Regulating PI3K/Akt/TNF-α Signaling Pathway
Objective:To explore the mechanism of Qiangzhi(QZ)Formula in the treatment of tic disorder(TD)based on PI3K/Akt/TNF-α signaling pathway.Methods:Forty-two SD rats were randomly divided into blank group,model group,tiapride group,and low-dose,medium-dose and high-dose QZ formula groups.The tic disorder model was established by intraperitoneal injection of iminodipropionitrile(IDPN).The low-dose,medium-dose and high-dose QZ formula groups were given 4.455 g/(kg·d),8.91 g/(kg·d)and 17.82 g/(kg·d)water decoction by gavage respectively.Tiapride group was given tiapride suspension 0.027 g/(kg·d)by gavage.The rats in the blank group and the model group were given the same dose of normal saline by gavage once a day for 28 consecutive days.The behavioral changes of rats were evaluated by stereotyped behavior score and motor behavior score.After the intervention,Western blot and qPCR were used to detect the mRNA and protein expression of PI3K,AKT and TNF-α in the striatum.The serum levels of IL-6 and TNF-α were detected by enzyme-linked reaction adsorption assay(ELISA).Results:After modeling,compared with the blank group,the rats in the model group showed abnormal motor behavior and stereotyped behavior.The protein expression levels of PI3K and TNF-α and the phosphorylation level of p-Akt/Akt increased in the striatum(P＜0.01,P＜0.01,P＜0.05);PI3K,Aktand mRNA expression levels increased(P＜0.001,P＜0.01,P＜0.05);and serum IL-6 and TNF-α levels increased(P＜0.001,P＜0.01).After 28 days of drug intervention,compared with the model group,the motor behavior score and stereotype-behavior score of tiapride group and AZ formula groups decreased(P＜0.001,P＜0.05).The expression levels of PI3K and TNF-α protein in striatum of QZ formula low-dose group decreased(P＜0.05).The expression levels of PI3K,Akt,TNF-α and p-Akt/Akt phosphorylation in the middle and high dose of QZ formula group decreased(P＜0.001,P＜0.05,P＜0.05).The expression levels of PI3K,Akt and mRNA in striatum of middle and high dose QZ formula group decreased(P＜0.01,P＜0.05).The level of serum IL-6 in tiapride group and QZ group decreased(P＜0.01,P＜0.001),and the serum TNF-α level decreased in each dose group of QZ formula(P＜0.01,P＜0.01,P＜0.05).Conclusions:Qiangzhi Formula can alleviate the abnormal motor behavior and stereotype behavior of rats with tic disorders,which may be related to the PI3K/Akt/TNF-α signaling pathway.
国家科技期刊平台
NSTL
万方数据
维普
