青蒿琥酯通过抑制NLRP3炎性小体信号通路对脂多糖诱导的急性呼吸窘迫综合征的保护作用

The Protective Effect of Artesunate on LPS-Induced Acute Respiratory Distress Syndrome through Inhibiting NLRP3 Inflammasome Signaling.

作者信息

Cui Yifei, Weng Wenbo, Ding Qing, Su Qinghua, Wang Xiaoying

机构信息

Department of Pharmacy, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China.

The Yuyao Health Further Education School, Ningbo, China.

出版信息

Evid Based Complement Alternat Med. 2022 Aug 23;2022:7655033. doi: 10.1155/2022/7655033. eCollection 2022.

BACKGROUND

Artesunate (AS) is a derivative of artemisinin that can exert anti-inflammatory effects. This study aims to explore the effect of AS on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS).

METHODS

The newborn mice were used for experimental ARDS model establishment by intraperitoneal injection of LPS (10 mg/kg) into mice with or without AS (20 mg/kg) pretreatment. After that, the pathological morphology of mouse lung tissue was observed by H&E staining. The content of inflammatory factors in serum was measured by ELISA and mRNA expression and lung tissue was determined by qRT-PCR. The expression of NLRP3 inflammasome and related proteins in lung tissue was confirmed by immunohistochemistry and Western blot.

RESULTS

AS treatment effectively alleviated the LPS-induced lung injury and pulmonary edema, and reduced the expression of IL-1, IL-18, IL-6, IL-8, MCP-1, and TNF- in serum and lung tissues of experimental ARDS mice. In addition, AS treatment reduced the expression of NLRP3, ASC, and caspase-1 in lung tissues of experimental ARDS mice.

CONCLUSION

AS alleviated LPS-induced lung injury in ARDS mice by inhibiting the activation of NLRP3 inflammasome.

背景

青蒿琥酯（AS）是青蒿素的衍生物，具有抗炎作用。本研究旨在探讨AS对脂多糖（LPS）诱导的急性呼吸窘迫综合征（ARDS）的影响。

方法

将新生小鼠用于实验性ARDS模型的建立，对小鼠腹腔注射LPS（10mg/kg），部分小鼠在注射前进行AS（20mg/kg）预处理。之后，通过苏木精-伊红（H&E）染色观察小鼠肺组织的病理形态。采用酶联免疫吸附测定（ELISA）法检测血清中炎症因子的含量，通过实时荧光定量聚合酶链反应（qRT-PCR）法检测肺组织中mRNA表达。通过免疫组织化学和蛋白质免疫印迹法确认肺组织中NLRP3炎性小体及相关蛋白的表达。

结果

AS治疗有效减轻了LPS诱导的肺损伤和肺水肿，并降低了实验性ARDS小鼠血清和肺组织中白细胞介素-1（IL-1）、白细胞介素-18（IL-18）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、单核细胞趋化蛋白-1（MCP-1）和肿瘤坏死因子-α（TNF-α）的表达。此外，AS治疗降低了实验性ARDS小鼠肺组织中NLRP3、凋亡相关斑点样蛋白（ASC）和半胱天冬酶-1（caspase-1）的表达。