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虫草素通过抑制NF-κB/p65诱导M1/M2巨噬细胞极化,减轻脓毒症未成熟小鼠的肝肺损伤和免疫缺陷。

Cordycepin induces M1/M2 macrophage polarization to attenuate the liver and lung damage and immunodeficiency in immature mice with sepsis via NF-κB/p65 inhibition.

作者信息

Zhang Yudan, Cheng Jing, Su Yufei, Li Mingyue, Wen Jun, Li Sixiu

机构信息

Department of Emergency, Xi'an Children's Hospital, Xi'an, Shaanxi, P.R. China.

Neonatal Intensive Care Unit, Xi'an Children's Hospital, Xi'an, Shaanxi, P.R. China.

出版信息

J Pharm Pharmacol. 2022 Feb 1;74(2):227-235. doi: 10.1093/jpp/rgab162.

DOI:10.1093/jpp/rgab162
PMID:34850068
Abstract

OBJECTIVES

To explore the impacts of cordycepin and underlying mechanism on the sepsis.

METHODS

The sepsis mice model was built and treated with different concentrations of cordycepin. Then the liver and lung injury caused by cecal ligation and puncture (CLP) was assessed using H&E staining and TUNEL assay. The expression of relevant genes was detected using qRT-PCR analysis and ELISA assays. Besides, the macrophage polarization was checked by flow cytometry.

KEY FINDINGS

Cordycepin could significantly improve the liver and lung injury. Moreover, cordycepin increased the distribution of F4/80+ CD206+ M2-like macrophages and F4/80+ iNOS+ M1-like macrophages through down-regulating the expression of relevant genes. More importantly, cordycepin could monitor the protein expression of iNOS, Arg-1, TNF-α, MCP-1, IL-4 and IL-10 in CLP mice. Meanwhile, the elevated level of p65 induced by CLP was also repressed by the increase of the cordycepin. Moreover, cordycepin played a crucial part in CLP mice through modulating the NF-κB/p65 signalling pathway.

CONCLUSIONS

Cordycepin played an important role in mice with sepsis via reducing the M1/M2 macrophage polarization and modulating the NF-κB/p65 signalling pathway.

摘要

目的

探讨虫草素对脓毒症的影响及其潜在机制。

方法

构建脓毒症小鼠模型,并用不同浓度的虫草素进行治疗。然后采用苏木精-伊红(H&E)染色和脱氧核糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法检测盲肠结扎穿孔(CLP)所致的肝肺损伤。采用实时荧光定量聚合酶链反应(qRT-PCR)分析和酶联免疫吸附测定(ELISA)检测相关基因的表达。此外,通过流式细胞术检测巨噬细胞极化情况。

主要发现

虫草素可显著改善肝肺损伤。此外,虫草素通过下调相关基因的表达,增加了F4/80+CD206+M2样巨噬细胞和F4/80+iNOS+M1样巨噬细胞的分布。更重要的是,虫草素可调控CLP小鼠中诱导型一氧化氮合酶(iNOS)、精氨酸酶-1(Arg-1)、肿瘤坏死因子-α(TNF-α)、单核细胞趋化蛋白-1(MCP-1)、白细胞介素-4(IL-4)和白细胞介素-10(IL-10)的蛋白表达。同时,CLP诱导的p65水平升高也被虫草素的增加所抑制。此外,虫草素通过调节核因子-κB/p65信号通路在CLP小鼠中发挥关键作用。

结论

虫草素通过减少M1/M2巨噬细胞极化和调节核因子-κB/p65信号通路,在脓毒症小鼠中发挥重要作用。

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