摘要
目的 采用TMT蛋白质组学研究黄芪甲苷对脓毒症小鼠肺组织蛋白组学的影响,为其临床应用治疗脓毒症提供科学依据.方法 采用盲肠结扎穿刺术(Cecal Ligation-Peferation,CLP)复制脓毒症小鼠模型,随机分为假手术组、模型组、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B细胞表达;提取肺组织蛋白,运用TMT蛋白质组学技术比较组间差异蛋白的表达,并进行生物信息学分析.结果 与假手术组比较,模型组肺组织炎症细胞浸润严重,结构塌陷;黄芪甲苷干预显著减轻脓毒症模型小鼠肺组织病理损伤.与模型组比较,黄芪甲苷药物干预组小鼠脾淋巴细胞B细胞(B220+)表达无明显影响(P＞0.05).TMT蛋白质组学结果分析肺组织蛋白差异成分,结果共鉴定出33个显著性差异蛋白,黄芪甲苷干预上调17个蛋白,下调16个蛋白.GO富集分析显示,黄芪甲苷主要干预生物功能过程,其中与脓毒症肺损伤密切相关差异主要蛋白是介导黏膜免疫的IgA产生通路.结论 黄芪甲苷对脓毒症诱导的肺损伤具有显著作用,其效应机制主要与干预B细胞分泌的IgA介导的黏膜免疫有关,该研究为黄芪临床治疗脓毒症奠定了基础.
Abstract
Objective:To study the effect of Astragaloside on lung tissue proteomics of sepsis mice by TMT pro-teomics and to provide scientific basis for its clinical application in the treatment of sepsis.Methods:The septic mouse models were replicated by Cecal Ligation-Peferation(CLP),and the mice were randomly divided into sham operation group,model group and Astragaloside group.H&E staining was used to detect the pathological injury of lung tissue.The expression of B cells was detected by flow cytometry.Lung tissue proteins were extracted,the expression of differ-ent proteins was compared by TMT proteomic technique,and bioinformatics analysis was performed.Results:Com-pared with the sham operation group,the model group had severe inflammatory cell infiltration and structural collapse.Astragaloside intervention significantly alleviated the pathological injury of lung tissue in sepsis model mice.Compared with that of the model group,the expression of splenic lymphocyte B cells(B220+)in the Astragaloside intervention group had no significant effect(P＞0.05).The results of TMT proteomic analysis showed that 33 different proteins were identified,among which 17 proteins were up-regulated and 16 proteins were down-regulated by Astragaloside.GO enrichment analysis showed that Astragaloside mainly interfered with biological functional processes,and the main protein closely related to lung injury in sepsis was IgA production pathway mediating mucosal immunity.Conclusion:Astragaloside has a significant effect on lung injury induced by sepsis,and its mechanism is mainly related to the inter-vention of IGA-mediated mucosal immunity secreted by B cells.This study lays a foundation for the clinical treatment of Astragaloside in sepsis.
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