银翘散加减对抽动障碍大鼠肺部菌群及外周-中枢炎症因子的影响OA

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.Patho-logical features of lung tissue and striatum were observed via HE staining.ELISA was used to measure the levels of inflammatory fac-tors TNF-α,IL-6,IL-1β,and IL-10 in bronchoalveolar lavage fluid,serum,and striatum.16S rRNA sequencing was adopted to ana-lyze 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 el-evated(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 indi-cated 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 el-evated(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.