Anti-Sepsis Immunological Mechanism of Astragaloside Ⅳ through Activating CD45 PTPase
Objective The aim of this study was designed to investigate the effect of Astragaloside Ⅳ on sepsis and its immunological mechanism.This study will provide a basis for the theoretical foundation of anti-sepsis immunotherapy of Astragalus.Methods CLP(Cecal ligation and puncture)model was established to investigated the anti-septic potential and reveal its underlying mechanisms,the mice with CLP were divide into five groups including sham group,model group,Astragaloside Ⅳ group,Anti-CD45 Ab group and Astragaloside Ⅱ+Anti-CD45 Ab group.Lung injury in sepsis mice was assessed by H&E staining.The percentage of Th1 cells(CD4+IFN-γ+)were detected by flow cytometry.The mRNA expression of Th1 cytokine and transcript factor T-bet were examined by q-PCR analysis.Results Compared with model group,treatment of Astragaloside Ⅳ can markedly improve the survival rate and reduce inflammatory lung injury in sepsis mice.However,anti-CD45 Ab treatment intensely blocked anti-septic effect including the enhanced survival rate and lung injure,which induced by Astragaloside Ⅳ.Furthermore,expression of Th1 cells(CD4+IFN-γ+)and Th1 cells related gene(IL-2、T-bet、STAT1、STAT4)mRNA expression were markedly increased in Astragaloside Ⅳ group comparison with model group.Whereas,the percentage of Th1 cells and Th1 cells related gene were significantly decreased in Astragaloside Ⅳ+Anti-CD45 Ab group.Conclusion Astragaloside Ⅳ might promote Th1 cell-mediated immune response in sepsis through CD45 protein tyrosine phosphatase activity.This mechanism will provide a basis for the clinical application of Astragalus in treating sepsis.
sepsisAstragaloside ⅣCD45 protein tyrosine phosphataseT1 help cellscecal ligation and puncture
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