miR-421靶向MPP7/EGFR/AKT轴影响巨噬细胞M2极化改善哮喘小鼠的气道炎症

doi:10.11958/20253182

天津医药 ›› 2026, Vol. 54 ›› Issue (5): 462-468.doi: 10.11958/20253182

miR-421靶向MPP7/EGFR/AKT轴影响巨噬细胞M2极化改善哮喘小鼠的气道炎症

卢红霞¹(), 郭燕军^2△(), 黄晗¹, 张婷¹

¹ 河南省儿童医院郑州儿童医院东三街院区呼吸科一病区（邮编 450000）
² 河南省儿童医院郑州儿童医院东三街院区呼吸科二病区（邮编 450000）

收稿日期:2025-10-17 修回日期:2025-12-24 出版日期:2026-05-15 发布日期:2026-05-13
通讯作者: ^△E-mail：15838106076@163.com
作者简介:卢红霞（1978），女，副主任医师，主要从事小儿内科学方面研究。E-mail：luhongxia399@163.com
基金资助:
河南省医学科技攻关计划联合共建项目(LHGJ20240549)

MiR-421 targeting the MPP7/EGFR/AKT axis to regulate macrophage M2 polarization and alleviating airway inflammation in asthmatic mice

LU Hongxia¹(), GUO Yanjun^2△(), HUANG Han¹, ZHANG Ting¹

¹ Ward 1 of Respiratory Department, East Third Street Campus of Henan Children's Hospital & Zhengzhou Children's Hospital, Zhengzhou 450000, China
² Ward 2 of Respiratory Department, East Third Street Campus of Henan Children's Hospital & Zhengzhou Children's Hospital, Zhengzhou 450000, China

Received:2025-10-17 Revised:2025-12-24 Published:2026-05-15 Online:2026-05-13
Contact: ^△E-mail：15838106076@163.com

卢红霞, 郭燕军, 黄晗, 张婷. miR-421靶向MPP7/EGFR/AKT轴影响巨噬细胞M2极化改善哮喘小鼠的气道炎症[J]. 天津医药, 2026, 54(5): 462-468.

LU Hongxia, GUO Yanjun, HUANG Han, ZHANG Ting. MiR-421 targeting the MPP7/EGFR/AKT axis to regulate macrophage M2 polarization and alleviating airway inflammation in asthmatic mice[J]. Tianjin Medical Journal, 2026, 54(5): 462-468.

摘要/Abstract

摘要：

目的探究miR-421影响巨噬细胞M2极化改善哮喘小鼠气道炎症的作用机制。方法将BALB/c小鼠随机分为对照组、哮喘组、mimic NC组、miR-421 mimic组、miR-421 mimic+OE-NC组、miR-421 mimic+OE-膜相关鸟苷酸激酶p55支架蛋白7（MPP7）组，每组12只。除对照组外，其他组小鼠均构建哮喘模型，建模成功后各干预处理1次，处理7 d后开始指标检测。qRT-PCR检测血清游离的miR-421表达及MPP7 mRNA表达；通过动物气道阻力与肺顺应性检测系统检测小鼠吸气阻力、呼气阻力、肺通气顺应性；酶联免疫吸附试验（ELISA）检测血清免疫球蛋白E（IgE）、白细胞介素（IL）-4、IL-13水平；HE染色观察肺组织变化；流式细胞术检测肺组织M2型巨噬细胞占比；Western blot检测肺组织精氨酸酶1（Arg-1）、MPP7、表皮生长因子受体（EGFR）、p-蛋白激酶B（AKT）/AKT蛋白；双萤光素酶报告基因实验验证miR-421与MPP7的靶向关系。结果与对照组比较，哮喘组小鼠气管壁增厚，相邻肺泡融合成囊腔，炎性细胞浸润明显，血清miR-421表达、肺通气顺应性降低，血清MPP7 mRNA表达、吸气阻力、呼气阻力、IgE、IL-4、IL-13、肺组织M2型巨噬细胞占比及Arg-1、MPP7、EGFR、p-AKT/AKT蛋白升高（P<0.05）；与哮喘组、mimic NC组比较，miR-421 mimic组对应指标变化趋势与上述相反（P<0.05）；OE-MPP7逆转了过表达miR-421对哮喘小鼠气道炎症的改善作用。结论过表达miR-421可能通过抑制MPP7/EGFR/AKT轴抑制巨噬细胞M2极化，进而改善哮喘小鼠的气道炎症。

关键词: 哮喘, 微RNAs, 鸟苷酸激酶类, ErbB受体, 原癌基因蛋白质c-akt, 巨噬细胞, M2极化, miR-421

Abstract:

Objective To investigate the mechanism by which miR-421 affects macrophage M2 polarization of macrophages and improves airway inflammation in asthmatic mice. Methods BALB/c mice were randomly divided into the control group, the asthma group, the mimic NC group, the miR-421 mimic group, the miR-421 mimic + OE-NC group and the miR-421 mimic + OE-Membrane-associated Guanylate Kinase p55 Scaffold Protein 7 (MPP7) group, with 12 mice in each group. Except for the control group, all other groups were subjected to establish asthma model. After successful modeling, each intervention was administered once, and indicators were assessed after 7 days. The expression levels of serum-free miR-421 and MPP7 mRNA were detected by qRT-PCR. Airway resistance and lung compliance were measured using a dedicated system. Serum levels of immunoglobulin E (IgE), interleukin (IL)-4 and IL-13 were determined by enzyme-linked immunosorbent assay (ELISA). Lung tissue morphology was assessed by HE staining. The proportion of M2-type macrophages in lung tissue was analyzed by flow cytometry. Western blot assay was used to detect the protein levels of Arginase-1 (Arg-1), MPP7, epidermal growth factor receptor (EGFR) and p-protein kinase B (AKT)/AKT in lung tissue. The targeting relationship between miR-421 and MPP7 was verified by dual-luciferase reporter assay. Results Compared with the control group, mice of the asthma group exhibited significant pathological changes: thickened tracheal walls, fused adjacent alveoli forming cystic cavities and obvious inflammatory cell infiltration. Furthermore, the asthma group showed decreased expression of serum miR-421 and lung dynamic compliance, while serum MPP7 mRNA, inspiratory resistance, expiratory resistance, IgE, IL-4, IL-13, the proportion of M2-type macrophages in lung tissue, and the protein expression of Arg-1, MPP7, EGFR and p-AKT/AKT were significantly increased (P<0.05). Compared with the asthma group and the mimic NC group, changes in the aforementioned indicators showed the opposite trends in the miR-421 mimic group (P<0.05). OE-MPP7 reversed the improvement effect of overexpression of miR-421 on airway inflammation in asthmatic mice. Conclusion Overexpression of miR-421 may inhibit macrophage M2 polarization by suppressing the MPP7/EGFR/AKT axis, thereby alleviating airway inflammation in asthmatic mice.

Key words: asthma, microRNAs, guanylate kinases, ErbB receptors, proto-oncogene proteins c-akt, macrophages, M2 polarization, miR-421

中图分类号:

R562.25

图/表 8

参考文献 20

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组别	miR-421	MPP7 mRNA
对照组	1.00±0.00	1.00±0.00
哮喘组	0.23±0.03^a	2.23±0.26^a
mimic NC组	0.25±0.02	2.25±0.21
miR-421 mimic组	0.89±0.08^bc	1.51±0.16^bc
miR-421 mimic+OE-NC组	0.91±0.09	1.53±0.18
miR-421 mimic+OE-MPP7组	0.90±0.08	1.91±0.19^de
F	410.900^＊＊	82.120^＊＊

组别	miR-421	MPP7 mRNA
对照组	1.00±0.00	1.00±0.00
哮喘组	0.23±0.03^a	2.23±0.26^a
mimic NC组	0.25±0.02	2.25±0.21
miR-421 mimic组	0.89±0.08^bc	1.51±0.16^bc
miR-421 mimic+OE-NC组	0.91±0.09	1.53±0.18
miR-421 mimic+OE-MPP7组	0.90±0.08	1.91±0.19^de
F	410.900^＊＊	82.120^＊＊

组别	吸气阻力/[cmH₂O/（s·mL）]	肺通气顺应性/（cmH₂O/mL）	呼气阻力/[cmH₂O/（s·mL）]
对照组	1.12±0.10	0.28±0.02	1.41±0.10
哮喘组	3.29±0.13^a	0.04±0.01^a	4.28±0.21^a
mimic NC组	3.31±0.12	0.05±0.01	4.30±0.22
miR-421 mimic组	1.46±0.11^bc	0.19±0.02^bc	2.05±0.12^bc
miR-421 mimic+OE-NC组	1.48±0.12	0.20±0.02	2.08±0.14
miR-421 mimic+OE-MPP7组	2.09±0.14^de	0.14±0.02^de	3.15±0.12^de
F	763.000^＊＊	345.600^＊＊	719.400^＊＊

组别	吸气阻力/[cmH₂O/（s·mL）]	肺通气顺应性/（cmH₂O/mL）	呼气阻力/[cmH₂O/（s·mL）]
对照组	1.12±0.10	0.28±0.02	1.41±0.10
哮喘组	3.29±0.13^a	0.04±0.01^a	4.28±0.21^a
mimic NC组	3.31±0.12	0.05±0.01	4.30±0.22
miR-421 mimic组	1.46±0.11^bc	0.19±0.02^bc	2.05±0.12^bc
miR-421 mimic+OE-NC组	1.48±0.12	0.20±0.02	2.08±0.14
miR-421 mimic+OE-MPP7组	2.09±0.14^de	0.14±0.02^de	3.15±0.12^de
F	763.000^＊＊	345.600^＊＊	719.400^＊＊

组别	IgE/（ng/L）	IL-4/（ng/L）
对照组	2.06±0.11	13.67±0.72
哮喘组	8.54±0.43^a	45.56±2.93^a
mimic NC组	8.59±0.44	45.51±2.88
miR-421 mimic组	3.57±0.19^bc	20.18±1.09^bc
miR-421 mimic+OE-NC组	3.59±0.22	20.21±1.07
miR-421 mimic+OE-MPP7组	5.69±0.31^de	30.67±1.68^de
F	954.900^＊＊	599.600^＊＊
组别	IL-13/ （ng/L）	M2型巨噬细胞占比/%
对照组	6.15±0.34	6.13±0.35
哮喘组	30.23±1.78^a	21.15±1.08^a
mimic NC组	29.98±1.63	21.11±1.06
miR-421 mimic组	8.89±0.51^bc	9.23±0.50^bc
miR-421 mimic+OE-NC组	8.92±0.53	9.25±0.51
miR-421 mimic+OE-MPP7组	15.58±0.83^de	16.63±0.87^de
F	1 192.000^＊＊	422.300^＊＊

miR-421靶向MPP7/EGFR/AKT轴影响巨噬细胞M2极化改善哮喘小鼠的气道炎症

MiR-421 targeting the MPP7/EGFR/AKT axis to regulate macrophage M2 polarization and alleviating airway inflammation in asthmatic mice

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参考文献 20

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组别	Arg-1/GAPDH			MPP7/GAPDH
对照组	0.72±0.06			0.51±0.05
哮喘组	2.16±0.19^a			1.43±0.15^a
mimic NC组	2.18±0.21			1.45±0.14
miR-421 mimic组	1.21±0.16^bc			0.78±0.06^bc
miR-421 mimic+OE-NC组	1.25±0.18			0.80±0.08
miR-421 mimic+OE-MPP7组	1.75±0.19^de			1.21±0.17^de
F	68.940^＊＊			65.070^＊＊
组别		EGFR/GAPDH	p-AKT/AKT
对照组		0.31±0.04	0.15±0.02
哮喘组		1.02±0.10^a	0.83±0.08^a
mimic NC组		1.03±0.11	0.85±0.08
miR-421 mimic组		0.52±0.06^bc	0.29±0.03^bc
miR-421 mimic+OE-NC组		0.54±0.05	0.31±0.03
miR-421 mimic+OE-MPP7组		0.79±0.07^de	0.46±0.04^de
F		89.110^＊＊	188.100^＊＊

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