梓醇调节cGAS-STING信号通路对创伤性脑损伤大鼠免疫功能的影响OA

Objective:To investigate the effects of Catalpol on the immune function and cyclic GMP-AMP synthase(cGAS)-stimulator of interferon gene(STING)signaling pathway in rats with traumatic brain injury(TBI).Methods:A TBI rat model was con-structed,and the modeled rats were randomly separated into TBI group,low-and high-dose treatment groups(Catalpol-L,Catalpol-H groups),and high-dose treatment+pathway activator group(Catalpol-H+2'3'-cGAMP group).Healthy normal rats were selected as the Control group.First,the neurological deficits of all experimental rats were evaluated.ELISA was applied to detect serum levels of inflammatory factors.Flow cytometry was applied to measure CD4+T and CD4+T/CD8+T levels.HE staining was applied to observe the morphology of brain tissue damage.Immunohistochemistry was applied to detect expressions of Iba-1 and Arg-1.Western blot was ap-plied to detect the expressions of cGAS-STING signaling pathway related proteins.Results:The brain tissue structure of the TBI group was disrupted compared to the Control group,with swelling and disordered arrangement of neuronal cells,decreased numbers,con-centrated and deeply stained nuclei,blurred nucleoli,and a large amount of inflammatory cell infiltration,the neurological deficit score,the levels of IL-6,TNF-α,and the expressions of CD8+T,Iba-1,cGAS,and p-STING/STING were elevated,the levels of CD4+T,CD4+/CD8+T,IL-4,IL-10,and the expression of Arg-1 were reduced(P<0.05).The brain tissue structure of the Catalpol-L and Catalpol-H groups were relatively normal compared with TBI group,with reduced neuronal pathological damage,relatively normal morphology,increased quantity,the inflammatory cell infiltration reduced,the neurological deficit score,the levels of IL-6,TNF-α,and expressions of CD8+T,Iba-1,cGAS and p-STING/STING were reduced,the levels of CD4+T,CD4+T/CD8+T,IL-4,IL-10,and the expression of Arg-1 were elevated(P<0.05).The Catalpol-H+2'3'-cGAMP group showed more severe brain tissue damage,abnor-mal neuronal morphology and disordered arrangement,decreased number,and increased inflammatory cell infiltration compared to the Catalpol-H group,the neurological deficit score,the levels of IL-6,TNF-α,and the expressions of CD8+T,Iba-1,cGAS,and p-STING/STING were elevated,the levels of CD4+T,CD4+T/CD8+T,IL-4,IL-10,and the expression of Arg-1 were reduced(P<0.05).Conclusion:Catalpol can improve the immune function of TBI rats,and its mechanism is related to the inhibition of the cGAS-STING pathway.