Behavior Improvement and Neuroprotective Effect of Tianma Gouteng Decoction on Tic Disorder Model Rats

OBJECTIVE To explore the improvement of Tianma Gouteng decoction(TGD) on the behavior of tic disorder (TD) rats and its neuroprotective machenism. METHODS Iminodipropionitrile induction solution was injected intraperitoneally to establish TD rat model, then rats were divided into TD group, thiopride group(4.2 mg·kg^-1), TGD low, medium, high dose group(19.6, 39.2, 78.4 g·kg^-1), normal rats were set into normal group, behavioral capacity of rats were measured after modeling. After 4-week treatment, behavioral capacity improvement of rats was evaluated. The striatum of rats in each group was isolated, and serum was collected, ELISA was used to detect the contents of dopamine(DA), tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β). HE staining was used to observe the pathological changes in the rat striatum, TUNEL staining was used to observe the neuronal apoptosis in the rat’s striatum, and Western blotting was used to determine the protein expressions of p-PI3K/PI3K, p-AKT/AKT, and p-GSK-3β/GSK-3β in the rats’t striatum. RESULTS After treatment, the stereotyped behavior, motor behavior and exercise ability of the TD rats were improved compared to those before treatment (P<0.01). And compared with TD group, pathological changes in each group were reduced; and content of DA, TNF-α, IL-1β in thiopride group and TGD medium, high-dose groups were significantly decreased(P<0.05 or P<0.01), the number of apoptotic neurons of striatum significantly decreased(P<0.05 or P<0.01), and the protein expressions of p-PI3K/PI3K and p-AKT/AKT were significantly increased(P<0.05 or P<0.01); the protein expressions of p-GSK-3β/GSK-3β in TGD medium, high-dose groups were significantly decreased(P<0.05 or P<0.01). CONCLUSION TGD improves the behavior of TD rats, and promotes the phosphorylation of PI3K/Akt/GSK-3β signaling pathway to exert neuroprotective effect, and its effect is dose-dependent.