黄芪甲苷调控CD45 PTPase介导抗脓毒症免疫机制的研究
Anti-Sepsis Immunological Mechanism of Astragaloside Ⅳ through Activating CD45 PTPase
杨海浩 1应赛 2顾茜兰 3邹楠婷 2吴招 2张春菲 2张浩洪 2万春平2
作者信息
- 1. 云南中医药大学,云南昆明 650500;云南经济管理学院,云南昆明 650106
- 2. 云南中医药大学,云南昆明 650500
- 3. 镇雄县中医医院,云南昭通 657200
- 折叠
摘要
目的 研究黄芪甲苷(Astragaloside Ⅳ,ASI Ⅳ)抗脓毒症效应及免疫学机制,为黄芪临床应用脓毒症治疗提供科学依据.方法 采用盲肠结扎穿刺术(Cecal ligation and puncture,CLP)构建脓毒症小鼠模型,随机分为假手术组、模型组、黄芪甲苷组、Anti-CD45单抗组、Anti-CD45单抗+黄芪甲苷组.H&E染色检测肺组织病理损伤;流式细胞术检测脾脏Th1细胞表达水平;实时荧光定量PCR(Real-time PCR)检测Th1细胞相关基因(IL-2、T-bet、STAT1和STAT4))mRNA的表达.结果 与模型组比较,黄芪甲苷干预显著提高脓毒症模型小鼠生存率,减轻模型小鼠肺组织病理损伤.CD45抗体干预后,阻断了黄芪甲苷提高生存率和减轻肺组织病理损伤的作用.机制研究结果表明,黄芪皂苷显著增加模型小鼠Th1细胞(CD4+IFN-γ+)比例,上调Th1细胞相关基因(IL-2、T-bet、STAT1、STAT4)mRNA表达,CD45抗体干预后,减少了黄芪甲苷促脾淋巴细胞Th1细胞比例,阻断黄芪皂苷促Th1细胞相关基因.结论 黄芪甲苷通过调控CD45分子,提高Th1细胞介导的免疫反应,介导抗脓毒症效应.
Abstract
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.
关键词
脓毒症/黄芪甲苷/CD45蛋白酪氨酸磷酸酶/Th1细胞/盲肠结扎穿孔术Key words
sepsis/Astragaloside Ⅳ/CD45 protein tyrosine phosphatase/T1 help cells/cecal ligation and puncture引用本文复制引用
出版年
2024
NETL
NSTL
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