Effect of trimetazidine on immune function in rats with Streptococcus pneumoniae pneumonia through cGAS-STING pathway.

Objective: To investigate effect of trimetazidine (TMZ) on immune function of Streptococcus pneumoniae (SP) pneumonia rats through cyclic guanylate adenylate synthase (cGAS)-stimulator of interferon gene (STING) pathway. Methods: Rats were randomly separated into model group, TMZ group and DMXAA group (cGAS-STING signaling pathway activator). SP pneumonia rat model was replicated by intranasal instillation of SP, while rats in control group were infused with an equal amount of physiological saline. ELISA was applied to detect IL-1β and IL-10 levels. Flow cytometry was applied to detect CD4*T and CD8*T levels. Spleen and thymus indexes of rats in each group were compared. Transmission turbidity method was applied to detect IgG and IgA levels. HE staining was applied to observe pathological changes in lung tissue. Western blot was applied to detect cGAS-STING pathway proteins expressions. Results: Compared with control group, rats in model group showed an increase in alveolar wall and lung interstitium, accompanied by edema, bleeding and inflammatory cell infiltration, IL-1β, CD8*T cells levels, lung tissue pathological injury score, cGAS, STING expressions were increased, IL-10, CD4*T cells levels, CD4*T/CD8*T, spleen and thymus indexes, IgG, IgA levels were decreased (P<0.05). Compared with model group, rats in TMZ group showed reduced thickening of alveolar walls, great improvement in alveolar structure, and less infiltration of inflammatory cells, IL-1β, CD8*T cells levels, lung tissue pathological injury score, cGAS, STING expressions were decreased, IL-10, CD4*T cells levels, CD4*T/CD8*T, spleen and thymus indexes, IgG, IgA levels were increased (P<0.05). Compared with TMZ group, IL-1(3, CD8*T levels, pathological injury score of lung tissue, cGAS and STING expressions in DMXAA group were increased, while IL-10, CD4*T cells levels, CD4*T/CD8*T, spleen and thymus index, IgG and IgA levels were decreased (P<0.05). Conclusion: TMZ may inhibit inflammation by inhibiting cGAS-STING signaling pathway, and enhance immune function of rats with SP pneumonia. [ABSTRACT FROM AUTHOR]