小白菊内酯通过调控铁死亡通路缓解模型大鼠脓毒症诱导的急性肺损伤

doi:10.16352/j.issn.1001-6325.2026.09.1207

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (9): 1207-1212.doi: 10.16352/j.issn.1001-6325.2026.09.1207

小白菊内酯通过调控铁死亡通路缓解模型大鼠脓毒症诱导的急性肺损伤

张露露, 田辉^*

武汉市中医医院汉阳院区急诊医学科, 湖北武汉 430000

收稿日期:2025-07-03 修回日期:2025-11-27 出版日期:2026-09-05 发布日期:2026-08-18
通讯作者: ^*rsmuf@163.com
基金资助:
武汉市中医药科研项目(WZ22C58)

Parthenolide alleviates sepsis-induced acute lung injury in rat models by regulating the ferroptosis pathway

ZHANG Lulu, TIAN Hui^*

Department of Emergency Medicine, Hanyang Branch of Wuhan Hospital of Traditional Chinese Medicine, Wuhan 430000, China

Received:2025-07-03 Revised:2025-11-27 Online:2026-09-05 Published:2026-08-18
Contact: ^*rsmuf@163.com

摘要/Abstract

摘要： 目的探究小白菊内酯(PTL)通过核因子E2相关因子2-谷胱甘肽过氧化物酶4(Nrf2-GPX4)铁死亡通路对脓毒症诱导的急性肺损伤(ALI)的影响。方法将大鼠随机分为对照组、ALI组[盲肠结扎穿孔(CLP)法构建大鼠ALI模型]、ALI+PTL组、ALI+Nrf2激动剂(SFN)组、ALI+PTL+Nrf2抑制剂(ML385)组。血气分析仪和肺湿/干重比分析血气指标和肺水肿情况;HE染色和Perls染色评估病理特征;ELISA、免疫荧光检测氧化应激和铁代谢指标;Western blot检测Nrf2-GPX4通路相关蛋白质水平。结果与ALI组比较,ALI+PTL组和ALI+SFN组大鼠动脉血氧分压(PaO₂)、超氧化物歧化酶(SOD)活性、谷胱甘肽过氧化物酶(GSH-Px)活性、GPX4阳性细胞率、p-Nrf2/Nrf2比值、GPX4蛋白水平上调,动脉血二氧化碳分压(PaCO₂)、肺湿/干重比、肺组织病理损伤评分、铁沉积面积百分比、4-羟基壬烯醛(4-HNE)含量、8-羟基脱氧鸟苷(8-OHdG)含量、酰基辅酶A合成酶长链家族成员4(ACSL4)阳性细胞率、铁蛋白(ferritin)阳性细胞率、血红素加氧酶-1(HO-1)蛋白水平下调(P＜0.05);与ALI+PTL组比较,ALI+PTL+ML385组可明显逆转上述指标(P＜0.05)。结论 PTL激活Nrf2-GPX4通路缓解脓毒症诱导的大鼠ALI。

关键词: 小白菊内酯, 铁死亡通路, 脓毒症, 急性肺损伤

Abstract: Objective To explore the effect of parthenolide (PTL) on sepsis-induced acute lung injury (ALI) through nuclear factor erythroid 2-related factor 2-glutathione peroxidase 4 (Nrf2-GPX4) ferroptosis pathway. Methods The cecal ligation and puncture (CLP) method was used to construct an ALI rat model. Rats were randomly divided into control group, ALI group, ALI+PTL group, ALI+Nrf2 agonist (SFN) group, and ALI+PTL+Nrf2 inhibitor (ML385) group. Blood gas indicators and pulmonary edema were evaluated by Blood gas analyzer and lung wet/dry weight ratio. HE staining and Perls staining microscopy were used to identify the pathological characteristics. ELISA and immunofluorescence were performed to measure oxidative stress and iron metabolism indicators. Western blot was performed to detect the Nrf2-GPX4 pathway related proteins. Results ALI group, ALI+PTL group and ALI+SFN group all showed up-regulation of partial arterial pressure of oxygen(PaO₂), superoxide dismutase(SOD) activity, glutathione peroxidase(GSH-Px) activity, glutathione peroxidase 4(GPX4) positive cell rate, p-Nrf2/Nrf2 ratio, and GPX4 protein, but down-regulation of partial arterial pressure of carbon dioxide(PaCO₂), lung wet/dry weight ratio, lung tissue pathological injury score, iron deposition area percentage, 4-hydroxynonenal(4-HNE) content, 8-hydroxy-2-deoxyguanosine(8-OHdG) content, acyl-CoA synthetase long-chain family member 4(ACSL4) positive cell rate, ferritin positive cell rate and heme oxygenase-1(HO-1) protein(P＜0.05). In ALI+PTL group and ALI+PTL+ML385 group indicators mentioned above were all significantly reversed(P＜0.05). Conclusions PTL alleviates sepsis-induced ALI by a mechanism of activation of Nrf2-GPX4 pathway.

Key words: parthenolide, ferroptosis pathway, sepsis, acute lung injury

中图分类号:

R563
R363.2

张露露, 田辉. 小白菊内酯通过调控铁死亡通路缓解模型大鼠脓毒症诱导的急性肺损伤[J]. 基础医学与临床, 2026, 46(9): 1207-1212.

ZHANG Lulu, TIAN Hui. Parthenolide alleviates sepsis-induced acute lung injury in rat models by regulating the ferroptosis pathway[J]. Basic & Clinical Medicine, 2026, 46(9): 1207-1212.

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小白菊内酯通过调控铁死亡通路缓解模型大鼠脓毒症诱导的急性肺损伤

Parthenolide alleviates sepsis-induced acute lung injury in rat models by regulating the ferroptosis pathway

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