Astragaloside IV reduces lung injury in lethal sepsis via promoting treg cells expansion and inhibiting inflammatory responses.
Astragaloside IV reduces lung injury in lethal sepsis via promoting treg cells expansion and inhibiting inflammatory responses.
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发表时间：
2023-11
影响因子：
0.8
通讯作者：
Haihao Yang;Na Yin;Qianlan Gu;Zhao Wu;Ying Xu;Jie Gao;Dongdong Qin;Chunping Wan
中科院分区：
文献类型：
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作者：
Haihao Yang;Na Yin;Qianlan Gu;Zhao Wu;Ying Xu;Jie Gao;Dongdong Qin;Chunping Wan
脓毒症是由感染进展为脓毒症相关器官衰竭（如肺损伤）引起的全身炎症反应综合征。黄芪甲苷（ASI-IV）是黄芪（Astragalus membranaceus，菲施）Bge（Huang-Qi）的主要活性成分之一，具有抗炎和免疫调节作用。然而，目前还不清楚ASI-IV是否可以通过激活调节性T细胞（TCFs）来减轻脓毒性肺损伤。本研究旨在评价ASI-IV对脓毒症肺损伤的治疗潜力，并进一步探讨其机制。在盲肠结扎穿孔（CLP）和脂多糖（LPS）诱导的脓毒症小鼠模型中，ASI-IV能显著提高小鼠的存活率，减轻炎症性肺损伤，通过减少骨髓细胞浸润和下调肺组织中IL-6和TNF-α的表达，保护小鼠免受加重的炎症反应。同时，ASI-IV治疗后Treg细胞相关基因表达，包括Foxp 3和IL-10，显著增加。ASI-IV能显著促进幼稚CD 4 + T细胞向调节性T细胞分化，但对Th 1和Th 17分化无明显影响。我们的结果表明，ASI-IV可以通过促进Treg细胞扩增和抑制炎症反应来减轻脓毒性肺损伤。它代表了一种有前途的药物用于治疗脓毒症。
Sepsis is a systemic inflammatory response syndrome caused by an infection progressing to sepsis-associated organ failure (such as lung injury). Our previous review revealed that Astragaloside IV (ASI-IV), one of the primary bioactive ingredients in Astragalus membranaceus (Fisch) Bge (Huang-Qi), had been shown to exert anti-inflammatory and immunomodulatory effects. Nevertheless, it is still unclear whether ASI-IV could attenuate septic lung injury via activating regulatory T-cells (Tregs). This study was designed to evaluate the therapeutic potential of ASI-IV on sepsis-induced lung injury and to further explore its underlying mechanism. In the murine models of cecal ligation and puncture (CLP) and lipopolysaccharide (LPS) induced sepsis, ASI-IV can markedly improve the survival rate and reduce inflammatory lung injury, protect mice against exacerbated inflammatory responses by decreasing myeloid cell infiltration and down-regulating IL-6 and TNF-α in lung tissue. Meanwhile, Treg cell-related gene expression, including Foxp3 and IL-10, significantly increased after ASI-IV treatment. Furthermore, ASI-IV notably promoted the differentiation of naïve CD4+ T cells into T regulatory cells without obviously affecting Th1 and Th17 differentiation. Our results indicated that ASI-IV could attenuate septic lung injury by promoting Treg cell expansion and inhibiting inflammatory responses. It represents a promising agent for the treatment of sepsis.