目的 基于NOD样受体热蛋白结构域相关蛋白3（NOD-like receptor thermal protein domain associated protein 3，NLRP3）炎症通路探讨滨蒿提取物（Artemisia scoparia extract，ASE）对急性肺损伤（acute lung injury，ALI）小鼠的保护作用及机制。方法 将ICR小鼠随机分为对照组、模型组及ASE低、中、高剂量（100、200、400 mg/kg）组和地塞米松（2.5 mg/kg）组，给予药物干预5 d。除对照组外，其余小鼠采用鼻腔内给予脂多糖（lipopolysaccharide，LPS）构建ALI模型，16 h后收集血清和肺组织。测定小鼠肺组织湿干质量比；采用苏木素-伊红（hematoxylin-eosin，HE）染色观察肺组织病理学变化；采用ELISA法测定血清中前列腺素E₂（prostaglandin E₂，PGE₂）、白三烯B₄（leukotriene B₄，LTB₄）以及肺组织中肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、单核细胞趋化蛋白-1（monocyte chemotactic protein-1，MCP-1）、白细胞介素-1β（interleukin-1β，IL-1β）含量；采用qRT-PCR检测肺组织TNF-α、MCP-1、IL-1β、NLRP3、半胱氨酸天冬氨酸蛋白酶-1（cystein-asparate protease-1，Caspase-1）、消皮素D（gasdermin D，GSDMD）的mRNA表达；采用Western blotting检测肺组织NLRP3、凋亡相关斑点样蛋白（apoptosis-associated speck，ASC）、Caspase-1、GSDMD蛋白表达。结果 与对照组比较，模型组小鼠肺组织结构异常，肺泡壁增厚，肺泡腔出血，肺泡周围炎性细胞增多，血清中PGE₂和LTB₄水平显著升高（P＜0.05），肺组织中TNF-α、MCP-1、IL-1β水平和mRNA表达水平显著升高（P＜0.01），肺组织中NLRP3、Caspase-1、GSDMD mRNA和蛋白表达水平显著上调（P＜0.01）。给予ASE干预后，上述指标明显改善（P＜0.05、0.01），且呈剂量相关性。结论 ASE对LPS诱导的小鼠ALI具有明显的保护作用，其作用机制可能为通过抑制NLRP3炎症小体信号通路减轻炎症反应，从而发挥抗ALI的作用。

Objective To investigate the mechanism of Artemisia scoparia extract (ASE) on acute lung injury (ALI) in mice based on NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome signaling pathway. Methods ICR mice were randomly divided into control group, model group, ASE low-, medium-, high-dose (100, 200, 400 mg/kg) groups and dexamethasone (2.5 mg/kg) group. Drugs were given for intervention of 5 d. Except for the control group, the remaining mice were induced with ALI model by intranasal administration of lipopolysaccharides (LPS), serum and lung tissue were collected 16 h later. Lung weight wet/dry ratio was measured. The pathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining. The contents of prostaglandin E₂ (PGE₂) and leukotriene B₄ (LTB₄) in serum, and the contents and mRNA expression levels of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-1β (IL-1β) in lung tissues were determined by ELISA. The mRNA expression levels of TNF-α, MCP-1, IL-1β, NLRP3, cystein-asparate protease-1 (Caspase-1) and gasdermin D (GSDMD) in lung tissues were detected by qRT-PCR. The protein expression levels of NLRP3, apoptosis-associated speck (ASC), Caspase-1, and GSDMD in lung tissues were detected by Western blotting. Results Compared with control group, model group showed abnormal lung tissue structure, thickened alveolar wall, bleeding alveolar cavity, inflammatory cell around the alveolar significantly increased. The levels of PGE₂ and LTB₄ in serum were significantly increased (P < 0.05), the levels and mRNA expression levels of TNF-α, MCP-1, IL-1β in lung tissue were significantly increased (P < 0.01), and the mRNA and protein expression levels of NLRP3, Caspase-1, and GSDMD in lung tissue were significantly up-regulated (P < 0.01). After ASE intervention, the above indicators were significantly improved (P < 0.05, 0.01) and showed a dose-dependent relationship. Conclusion ASE has a significant protective effect on LPS-induced ALI in mice, which may be related to reduce inflammatory response by inhibiting NLRP3 inflammasome signaling pathway.

R285.5

新疆维吾尔自治区创新环境（人才、基地）建设专项（PT2305）；新疆维吾尔自治区自然科学基金项目（2021D01A163）