OBJECTIVE To investigate the potential mechanisms of modified Yinqiao San in treating tic disorders (TD).

METHODS Forty-eight SPF-grade SD rats were randomly divided into a control group (Control, n=8) and a modeling group (n=40). An external pathogenic wind-induced TD rat model was established using 3,3'-iminodipropionitrile (IDPN) combined with alternating cold-hot stimulation. After successful modeling, the rats were re-randomized into five groups (n=8 each): model group (Model), tiapride group (Tiapride), and modified Yinqiao San high-, medium-, and low-dose groups (YQS-H, YQS-M, YQS-L). The tiapride group received 47.91 mg·kg⁻¹·d⁻¹ of tiapride solution, while the YQS-H, YQS-M, and YQS-L groups received 17.64, 8.82, and 4.41 g·kg⁻¹·d⁻¹ of YQS solution, respectively, for 12 consecutive days. After the last dose, tic-like behaviors were evaluated. Pathological features of lung tissue and striatum were observed via HE staining. ELISA was used to measure the levels of inflammatory factors TNF-α, IL-6, IL-1β, and IL-10 in bronchoalveolar lavage fluid, serum, and striatum. 16S rRNA sequencing was adopted to analyze microbiota structures in the upper respiratory tract (pharyngeal swabs) and lower respiratory tract (bronchoalveolar lavage fluid).

RESULTS Compared to the Control group, the Model group showed increased tic behavior scores (P<0.01), elevated total movement distance and velocity, and significantly reduced resting time (P<0.01). HE staining revealed thickened alveolar walls, collapsed and deformed alveoli, interstitial pulmonary edema, and inflammatory cell infiltration. The striatal neuronal cell count decreased, with sparse and disorganized Nissl bodies. Levels of TNF-α, IL-6, and IL-1β in bronchoalveolar lavage fluid, serum, and striatum were elevated (P<0.01), while IL-10 levels decreased (P<0.01). Compared to the Model group, the Tiapride group, YQS-H group, and YQS-M group exhibited reduced tic behavior scores, total movement distance, and velocity, along with increased resting time (P<0.05, P<0.01). Both YQS-H and YQS-M groups demonstrated significant improvements in lung tissue damage, decreased pathological scores (P<0.01), increased Nissl body counts (P<0.01), partial alleviation of disorganized arrangements, reduced levels of TNF-α, IL-6, and IL-1β in bronchoalveolar lavage fluid, serum, and striatum (P<0.01), and elevated IL-10 levels (P<0.01). The 16S rRNA results indicated that compared to the Control group, the relative abundance of the genus Veillonella in the upper respiratory tract was increased in the Model group (P<0.05), while the relative abundance of the genus Klebsiella in the lower respiratory tract microbiota was also elevated (P<0.05). All YQS dosage groups were able to reduce the levels of Veillonella and Klebsiella (P<0.05).

CONCLUSION Modified Yinqiao San can improve tic-like behavior in TD model rats. Its possible mechanism is related to regulating lung microbiota structure and alleviating peripheral and central inflammation.