槐杞黄调控Jun/SLC7A11介导的气道上皮细胞铁死亡抑制哮喘大鼠气道重塑及胶原沉积

doi:10.11958/20260423

天津医药 ›› 2026, Vol. 54 ›› Issue (9): 902-907.doi: 10.11958/20260423

槐杞黄调控Jun/SLC7A11介导的气道上皮细胞铁死亡抑制哮喘大鼠气道重塑及胶原沉积

刘琳琳(), 梁冬雪, 刘丽华, 田颖, 孙丽丽^△()

锦州医科大学附属第一医院呼吸危重症监护病房（邮编 121000）

收稿日期:2026-02-05 修回日期:2026-04-28 出版日期:2026-09-15 发布日期:2026-09-14
通讯作者: ^△E-mail：278800539@qq.com
作者简介:刘琳琳（1990），女，主治医师，主要从事呼吸系统疾病诊治方面研究。E-mail：liulinlin2011@sina.cn
基金资助:
锦州市指导性科技计划项目(JZ2025B028)

Huaiqihuang regulating Jun/SLC7A11-mediated airway epithelial cell ferroptosis to inhibit airway remodeling and collagen deposition in asthmatic rats

LIU Linlin(), LIANG Dongxue, LIU Lihua, TIAN Ying, SUN Lili^△()

Department of Respiratory Intensive Care Unit, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121000, China

Received:2026-02-05 Revised:2026-04-28 Published:2026-09-15 Online:2026-09-14
Contact: ^△E-mail：278800539@qq.com

刘琳琳, 梁冬雪, 刘丽华, 田颖, 孙丽丽. 槐杞黄调控Jun/SLC7A11介导的气道上皮细胞铁死亡抑制哮喘大鼠气道重塑及胶原沉积[J]. 天津医药, 2026, 54(9): 902-907.

LIU Linlin, LIANG Dongxue, LIU Lihua, TIAN Ying, SUN Lili. Huaiqihuang regulating Jun/SLC7A11-mediated airway epithelial cell ferroptosis to inhibit airway remodeling and collagen deposition in asthmatic rats[J]. Tianjin Medical Journal, 2026, 54(9): 902-907.

摘要/Abstract

摘要：

目的观察槐杞黄通过调控气道上皮细胞铁死亡对哮喘大鼠气道重塑及胶原沉积的抑制作用并探讨其机制。方法 60只大鼠随机分为正常组、哮喘组、低剂量组、高剂量组、高剂量+抑制剂组，每组12只。除正常组外，其余各组采用卵清蛋白（OVA）致敏与雾化激发建立哮喘模型，剔除造模失败大鼠，最终每组纳入10只。低、高剂量组从首次OVA激发当日开始，分别每日灌胃槐杞黄溶液3.6、7.2 g/kg，高剂量+抑制剂组在给予高剂量槐杞黄的同时腹腔注射柳氮磺吡啶150 mg/kg。正常组、哮喘组每日灌胃等体积生理盐水。比较各组肺功能及肺组织丙二醛（MDA）、还原型谷胱甘肽（GSH）、活性氧（ROS）含量；HE染色、Masson染色检测气道壁、气道平滑肌及胶原纤维沉积厚度；Western blot法检测肺组织p-Jun/Jun及溶质载体家族7成员11（SLC7A11）、谷胱甘肽过氧化物酶4（GPX4）蛋白表达量。结果低剂量组气道阻力（RL）及肺组织MDA、ROS含量及p-Jun/Jun均低于哮喘组，高剂量组均低于低剂量组，高剂量+抑制剂组均高于高剂量组（均P<0.05）；低剂量组肺动态顺应性（Cdyn）、肺组织GSH含量及SLC7A11、GPX4蛋白表达量均高于哮喘组，高剂量组均高于低剂量组，高剂量+抑制剂组均低于高剂量组（P<0.05）。低剂量组气道壁、气道平滑肌及胶原纤维沉积厚度均小于哮喘组，高剂量组均小于低剂量组，高剂量+抑制剂组均大于高剂量组（均P<0.05）。结论槐杞黄可抑制哮喘大鼠气道重塑及胶原沉积，其机制可能与抑制Jun活化、上调SLC7A11表达、从而减轻气道上皮细胞铁死亡有关。

关键词: 哮喘, 铁死亡, 气道重塑, 胶原, 原癌基因蛋白质c-jun, 溶质载体蛋白质类, 槐杞黄

Abstract:

Objective To observe the inhibitory effect of Huaiqihuang on airway remodeling and collagen deposition in asthmatic rats by regulating airway epithelial cell ferroptosis, and to explore the possible mechanism. Methods Sixty rats were randomly divided into the normal group, the asthma group, the low-dose group, the high-dose group and the high-dose + inhibitor group, with 12 rats in each group. Except for the normal group, asthma models were established in the other groups by ovalbumin (OVA) sensitization and nebulized challenge. Rats with unsuccessful modeling were excluded, and finally 10 rats were included in each group. Rats in the low-dose group and the high-dose group, starting from the day of the first OVA challenge, received daily intragastric administration of Huaiqihuang solution at 3.6 g/kg and 7.2 g/kg, respectively. Rats of the high-dose + inhibitor group received high-dose Huaiqihuang and intraperitoneal injection of sulfasalazine (150 mg/kg). Rats of the normal group and the asthma group received daily intragastric administration of an equal volume of normal saline. Lung function and the contents of malondialdehyde (MDA), glutathione (GSH) and reactive oxygen species (ROS) in lung tissue were compared between groups. HE staining and Masson staining were used to measure the thickness of airway wall, airway smooth muscle and collagen fiber deposition. Western blot assay was used to detect the protein expression of p-Jun/Jun, solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in lung tissue. Results Airway resistance (RL), MDA and ROS contents in lung tissue, and p-Jun/Jun ratio were lower in the low-dose group than those in the asthma group, and those in the high-dose group were lower than those in the low-dose group. And those in the high-dose + inhibitor group were higher than those in the high-dose group (all P<0.05). Lung dynamic compliance (Cdyn), GSH content in lung tissue, and protein expression of SLC7A11 and GPX4 were higher in the low-dose group than those in the asthma group, those in the high-dose group were higher than those in the low-dose group, and those in the high-dose + inhibitor group were lower than those in the high-dose group (all P<0.05). The thicknesses of airway wall, airway smooth muscle and collagen fiber deposition were less in the low-dose group than those in the asthma group, those in the high-dose group were less than those in the low-dose group, and those in the high-dose + inhibitor group were greater than those in the high-dose group (all P<0.05). Conclusion Huaiqihuang can inhibit airway remodeling and collagen deposition in asthmatic rats, and its mechanism may be related to the inhibition of Jun activation, up-regulation of SLC7A11 expression, and thereby the alleviation of ferroptosis of airway epithelial cells.

Key words: asthma, ferroptosis, airway remodeling, collagen, proto-oncogene proteins c-jun, solute carrier proteins, Huaiqihuang

中图分类号:

R563.9

图/表 7

表1 各组肺功能指标比较（n=10，$\bar{x}\pm s$）

Tab.1 Comparison of pulmonary function indicators between different groups

组别	RL/（cmH₂O·s·mL^-1）	Cdyn/（mL/cmH₂O）
正常组	0.24±0.05	0.61±0.13
哮喘组	0.88±0.18^a	0.27±0.06^a
低剂量组	0.67±0.13^b	0.41±0.09^b
高剂量组	0.47±0.09^bc	0.56±0.11^bc
高剂量+抑制剂组	0.72±0.14^d	0.36±0.07^d
F	38.473^＊＊	20.841^＊＊

表2 各组肺组织MDA、GSH、ROS含量比较（n=10，$\bar{x}\pm s$）

Tab.2 Comparison of MDA, GSH and ROS contents in lung tissue between the five groups

组别	MDA/（nmol/mg）	GSH/（μmol/g）	ROS
正常组	2.35±0.43	12.49±2.27	158.46±18.27
哮喘组	6.90±1.12^a	5.19±1.34^a	387.55±42.59^a
低剂量组	5.21±1.03^b	7.96±1.67^b	265.41±31.56^b
高剂量组	3.47±0.65^bc	10.65±2.09^bc	209.78±25.92^bc
高剂量+抑制剂组	4.96±0.93^d	7.17±1.38^d	245.79±40.83^d
F	40.011^＊＊	26.007^＊＊	66.379^＊＊

图1 各组大鼠肺组织HE染色观察气道病理改变（×200） A：正常组；B：哮喘组；C：低剂量组；D：高剂量组；E：高剂量+抑制剂组；标尺50 μm。图2、3同。

Fig.1 Airway epithelial damage, inflammatory infiltration and airway wall thickening in lung tissue of each group of rats observed by HE staining (×200)

图2 各组大鼠肺组织Masson染色观察胶原纤维沉积情况（×200）

Fig.2 Collagen fiber deposition in lung tissue of each group of rats observed by Masson staining (Masson staining, ×200)

表3 各组气道壁、气道平滑肌及胶原纤维沉积厚度比较（n=10，μm，$\bar{x}\pm s$）

Tab.3 Comparison of the deposition thickness of airway walls, airway smooth muscle and collagen fibers between five groups

组别	气道壁厚度	气道平滑肌厚度	胶原纤维沉积厚度
正常组	11.49±2.09	5.09±0.98	3.67±0.69
哮喘组	26.35±4.86^a	7.54±1.37^a	5.82±1.12^a
低剂量组	19.54±3.41^b	5.97±1.03^b	4.49±0.87^b
高剂量组	14.36±2.58^bc	4.93±0.98^bc	3.54±0.62^bc
高剂量+抑制剂组	18.54±3.43^d	5.99±1.04^d	4.38±0.91^d
F	27.493^＊＊	8.972^＊＊	11.048^＊＊

表4 各组肺组织p-Jun/Jun及SLC7A11、GPX4蛋白表达量比较（n=10，$\bar{x}\pm s$）

Tab.4 Comparison of protein expression levels of p-Jun/Jun, SLC7A11 and GPX4 in lung tissue between five groups

组别	p-Jun/Jun	SLC7A11	GPX4
正常组	0.12±0.03	0.92±0.08	0.98±0.07
哮喘组	0.96±0.07^a	0.16±0.03^a	0.34±0.05^a
低剂量组	0.79±0.06^b	0.42±0.04^b	0.51±0.06^b
高剂量组	0.42±0.05^bc	0.56±0.07^bc	0.75±0.08^bc
高剂量+抑制剂组	0.81±0.07^d	0.21±0.03^d	0.49±0.05^d
F	377.516^＊＊	335.744^＊＊	158.349^＊＊

图3 Western blot检测各组大鼠肺组织Jun、p-Jun、SLC7A11、GPX4蛋白表达量

Fig.3 Expression levels of Jun, p-Jun, SLC7A11 and GPX4 proteins in lung tissue between five groups of rats detected by Western blot assay

参考文献 21

[1]	GBD 2021 Asthma and Allergic Diseases Collaborators. Global,regional,and national burden of asthma and atopic dermatitis,1990-2021,and projections to 2050:a systematic analysis of the Global Burden of Disease Study 2021[J]. Lancet Respir Med, 2025, 13(5):425-446. doi:10.1016/S2213-2600(25)00003-7.
[2]	Varricchi G, Brightling C E, Grainge C, et al. Airway remodelling in asthma and the epithelium:on the edge of a new era[J]. Eur Respir J, 2024, 63(4):2301619. doi:10.1183/13993003.01619-2023.
[3]	Rayner D G, Ferri D M, Guyatt G H, et al. Inhaled reliever therapies for asthma:a systematic review and meta-analysis[J]. JAMA, 2025, 333(2):143-152. doi:10.1001/jama.2024.22700.
[4]	Yamada K, St Croix C, Stolz D B, et al. Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes[J]. Nat Commun, 2024, 15(1):5818. doi:10.1038/s41467-024-50222-2.
[5]	He R, Wei Y, Peng Z, et al. α-Ketoglutarate alleviates osteoarthritis by inhibiting ferroptosis via the ETV4/SLC7A11/GPX4 signaling pathway[J]. Cell Mol Biol Lett, 2024, 29(1):88. doi:10.1186/s11658-024-00605-6.
[6]	曲艳春, 刘贵昌. 槐杞黄颗粒联合小青龙汤对哮喘缓解期肺脾气虚证患儿免疫功能及预后的影响分析[J]. 中华中医药学刊, 2025, 43(5):44-47.
	Qu Y C, Liu G C. Effect of huaiqihuang granule combined with xiaoqinglong decoction on immune function and prognosis of qi deficiency of lung and spleen syndrome in remission stage of asthma[J]. Chinese Archives of Traditional Chinese Medicine, 2025, 43(5):44-47. doi:10.13193/j.issn.1673-7717.2025.05.010.
[7]	韦嘉慧, 雷凤英, 黄藓慧, 等. 基于Th1/Th2平衡探讨槐杞黄颗粒对阿霉素致肾病综合征大鼠的治疗作用[J]. 山东医药, 2025, 65(8):42-47.
	Wei J H, Lei F Y, Huang X H, et al. Therapeutic effect of Huaiqihuang granules on rats with adriamycin-induced nephrotic syndrome based on Th1/Th2 balance[J]. Shandong Medical Journal, 2025, 65(8):42-47. doi:10.3969/j.issn.1002-266X.2025.08.009.
[8]	Varricchi G, Poto R, Lommatzsch M, et al. Biologics and airway remodeling in asthma:early,late,and potential preventive effects[J]. Allergy, 2025, 80(2):408-422. doi:10.1111/all.16382.
[9]	Tiotiu A. Airway remodeling in asthma[J]. Open Respir Arch, 2024, 7(1):100384. doi:10.1016/j.opresp.2024.100384.
[10]	Agache I, Adcock I M, Baraldi F, et al. Personalized therapeutic approaches for asthma[J]. J Allergy Clin Immunol, 2025, 156(3):503-522. doi:10.1016/j.jaci.2025.03.025.
[11]	Tang Y F, Xie W Y, Wu HY, et al. Huaier polysaccharide alleviates dextran sulphate sodium salt-induced colitis by inhibiting inflammation and oxidative stress,maintaining the intestinal barrier,and modulating gut microbiota[J]. Nutrients, 2024, 16(9):1368. doi:10.3390/nu16091368.
[12]	黄伟, 李倩, 朱继田. 基于Nrf2/GPX4通路研究枸杞多糖对缺氧/复氧诱导的心肌细胞铁死亡的影响[J]. 中草药, 2025, 56(10):3568-3576.
	Huang W, Li Q, Zhu J T. Effect of Lycium barbarum polysaccharides on hypoxia/reoxygenation-induced ferroptosis in cardiomyocytes based on Nrf2/GPX4 pathway[J]. Chinese Traditional and Herbal Drugs, 2025, 56(10):3568-3576. doi:10.7501/j.issn.0253-2670.2025.10.015.
[13]	Qin Y, Zhao G, Wang Z, et al. Polygonatum sibiricum polysaccharide attenuates cyclophosphamide-induced testicular damages and sperm defects in male mice via Nrf2 mediating antioxidant protective mechanisms[J]. Int J Biol Macromol, 2025, 307(Pt3):141968. doi:10.1016/j.ijbiomac.2025.141968.
[14]	尹小梅, 袁珂, 晁爽. 槐杞黄颗粒辅助治疗幼儿及学龄前儿童支气管哮喘的临床研究[J]. 中国临床药理学杂志, 2023, 39(10):1371-1375.
	Yin X M, Yuan K, Chao S. Clinical trial of Huaiqihuang granules in adjuvant treatment of bronchial asthma in young children and preschool children[J]. Chinese Journal of Clinical Pharmacology, 2023, 39(10):1371-1375. doi:10.13699/j.cnki.1001-6821.2023.10.001.
[15]	Chen J, He Y, Chen R, et al. SLC7A11 in fibrosis:molecular mechanisms and future prospects[J]. Aging Dis, 2025, 17(2):731-759. doi:10.14336/AD.2025.0106.
[16]	Zhang M, Zheng H, Zhu X, et al. Synchronously evoking disulfidptosis and ferroptosis via systematical glucose deprivation targeting SLC7A11/GSH/GPX4 antioxidant axis[J]. ACS Nano, 2025, 19(14):14233-14248. doi:10.1021/acsnano.5c00730.
[17]	Guo X, Wang C, Yu X, et al. Cold exposure exacerbates allergic airway inflammation via ferroptosis:evidence from a murine model[J]. Antioxidants (Basel), 2025, 15(1):32. doi:10.3390/antiox15010032.
[18]	Jiang L, Xu L, Liu H, et al. Rhizoma dioscoreae nipponicae relieves asthma by inducing the ferroptosis of eosinophils and inhibiting the p38 MAPK signaling pathway[J]. Crit Rev Immunol, 2024, 44(2):77-87. doi:10.1615/CritRevImmunol.2023050922.
[19]	王玲, 史晓光, 高爽, 等. 槐耳多糖通过p53/SLC7A11/GPX4信号轴促进三阴乳腺癌细胞铁死亡的机制研究[J]. 现代中西医结合杂志, 2025, 34(8):1023-1028,1056.
	Wang L, Shi X G, Gao S, et al. Mechanism of Huaier polysaccharide promoting ferroptosis in triple-negative breast cancer cells via the p53/SLC7A11/GPX4 signaling axis[J]. Modern Journal of Integrated Traditional Chinese and Western Medicine, 2025, 34(8):1023-1028,1056. doi:10.3969/j.issn.1008-8849.2025.08.001.
[20]	邱政皓, 马雅萍, 马昌盛, 等. 枸杞多糖通过SLC7A11/GPX4通路抑制铁死亡减轻小鼠脑缺血再灌注损伤[J]. 神经解剖学杂志, 2024, 40(5):607-612.
	Qiu Z H, Ma Y P, Ma C S, et al. Lycium barbarum polysaccharide inhibits iron death through SLC7A11/GPX4 pathway to reduce cerebral ischemia-reperfusion injury in mice[J]. Chinese Journal of Neuroanatomy, 2024, 40(5):607-612. doi:10.16557/j.cnki.1000-7547.2024.05.011.
[21]	曾启航, 常笑语, 刘伦静, 等. 枸杞多糖通过Nrf2/GPX4途径抑制铁死亡改善热射病大鼠结肠损伤[J]. 宁夏医科大学学报, 2024, 46(5):446-452.
	Zeng Q H, Chang X Y, Liu L J, et al. LBP attenuate heat stroke-induced colonic injury in rats by inhibiting ferroptosis through Nrf2/GPX4 pathway[J]. Journal of Ningxia Medical University, 2024, 46(5):446-452. doi:10.16050/j.cnki.issn1674-6309.2024.05.003.

槐杞黄调控Jun/SLC7A11介导的气道上皮细胞铁死亡抑制哮喘大鼠气道重塑及胶原沉积

Huaiqihuang regulating Jun/SLC7A11-mediated airway epithelial cell ferroptosis to inhibit airway remodeling and collagen deposition in asthmatic rats

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