Study on the mechanism of T cell dysfunction alleviated by Picria felterrae extractive in burn sepsis mice model
Objective To explore whether the Picria felterrae extractive(PFE)can alleviate the symptoms of mice with burn sepsis by regulating the FMS like tyrosine kinase 3 ligand(Flt3L)and its regulation effect on T cell function.Methods The study was conducted from July 2022 to April 2023 at the animal experimental center of Ankang Traditional Chinese Medicine Hospital.According to the random number table method,72 SPF male C57 mice[body mass 21-25(22±2)g,10 weeks old]were randomly divided into 6 groups:a burn group,a model group,low,middle,and high dose of PFE groups,and a positive group.The low,middle,and high dose of PFE groups were given 0.5 g/kg,1.0 g/kg,and 2.0 g/kg of PFE on the next day after model preparation for 1 week.In the positive group,10 μg of Flt3L was injected subcutaneously on the next day after model preparation for 9 days.The fluorescence intensity of the back skin was detected on day 1,3,and 5 after administration;the levels of serum interleukin(IL)-6,IL-1β,tumor necrosis factor α(TNF-α),proliferation activity of peripheral blood T lymphocytes,changes of spleen T-lymphocyte subsets,histopathological changes of subcutaneous tissue,lung,and spleen,and expression levels of IL-2,IL-4,interferon-y(IFN-y),and Flt3L protein were detected.Univariate analysis of variance and SNK-q test were used for statistical analysis.Results Compared with the burn group,the fluorescence intensity of the wound bacteria in the model group was enhanced,and the levels of IL-6[(59.44±5.41)μg/L vs.(23.47±3.29)μg/L],IL-1β[(80.47±6.83)μg/L vs.(32.74±4.36)μg/L],and TNF-α[(12.33±1.15)μg/L vs.(4.76±0.97)μg/L],pathology scores of wound tissue,lung tissue,and spleen tissue,IL-2,IL-4,and IFN-y protein expressions,and CD8+T cell proportion[(65.33±5.68)%vs.(26.72±6.75)%]in the model group were all higher,but the T lymphocyte proliferation activity,CD3+T cell proportion[(34.55±3.29)%vs.(64.49±9.33)%],CD4+T cell proportion[(16.71±3.49)%vs.(48.18±7.36)%],and CD4+/CD8+[(0.26±0.06)vs.(1.81±0.35)]were all lower(all P<0.05).Compared with the model group,the fluorescence intensities of the wound bacteria in the low,middle,and high dose of PFE groups and the positive group were weakened,and the levels of IL-6,IL-1β,and TNF-α,pathology scores of wound tissue,lung tissue,and spleen tissue,IL-2,IFN-y,and IL-4 protein expressions,and CD8+T cell proportion were all lower,but the T lymphocyte proliferation activity,CD3+T,CD4+T,and CD4+/CD8+were all higher,in dose-dependent manners(all P<0.05).Conclusion PFE can reduce the bacterial content of infected wound,inflammation,and organ damage,and the mechanism may be related to up-regulation of Flt3L,promotion of T lymphocyte activity,and remission of immunosuppression.
SepsisBurnPicria felterrae extractiveFMS like tyrosine kinase 3 ligandAnimal experiment