中国临床药理学杂志

奥马珠单抗通过miR-26a-5p减少炎症小体NLRP3介导的焦亡对哮喘大鼠气道重塑的影响

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莫俊俏 ¹ , 赵桂铃 ¹ , 焦瀚仪 ^2a , 孔德志 ^2a , 张全鹏 ^2b

中国临床药理学杂志 | 临床与基础桥接研究 2025,41(6): 816-821

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中国临床药理学杂志 |临床与基础桥接研究 2025 , 41 (6) : 816 -821

奥马珠单抗通过miR-26a-5p减少炎症小体NLRP3介导的焦亡对哮喘大鼠气道重塑的影响

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莫俊俏¹, 赵桂铃¹, 焦瀚仪^2a, 孔德志^2a, 张全鹏^2b

作者信息

^1.海南省第五人民医院药剂科，海南海口 570206

^2a.海南医科大学，生理学教研室，海南海口 571199

^2b.海南医科大学，人体解剖学实验室，海南海口 571199

通讯作者:

张全鹏，教授，硕士生导师 MP: 18889790750 E-mail: 510056952@qq.com

作者简介:

莫俊俏（1988-），女，主管药师，主要从事医院药事管理和质控方面的工作

Effects of omalizumab on airway remodeling in asthmatic rats by reducing inflammatory vesicle NLRP3-mediated pyroptosis via miR-26a-5p

Jun-qiao MO¹, Gui-ling ZHAO¹, Han-yi JIAO^2a, De-zhi KONG^2a, Quan-peng ZHANG^2b

Affiliations

^1.Department of Pharmacy, The Fifth People’s Hospital of Hainan Province, Haikou 570206, Hainan Province, China

^2a.Physiology Section, Hainan Medical University, Haikou 571199, Hainan Province, China

^2b.Human Anatomy Laboratory, Hainan Medical University, Haikou 571199, Hainan Province, China

出版时间: 2025-03-28 doi: 10.13699/j.cnki.1001-6821.2025.06.013

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摘要

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目的

基于抑制Toll样受体4（TLR4）/髓样分化因子88（MyD88）/核因子κB（NF-κB）信号通路探讨奥马珠单抗通过微小RNA（miR）-26a-5p减少炎症小体即核苷酸结合寡聚结构域样受体蛋白3（NLRP3）介导的焦亡对哮喘大鼠气道重塑的影响机制。

方法

将50只SD大鼠分为对照组、模型组、奥马珠单抗组、奥马珠单抗+agomir NC组和奥马珠单抗+miR-26a-5p agomir组，每组10只。对照组腹腔注射0.9% NaCl；模型组建立哮喘模型；奥马珠单抗组在模型组的基础上每日腹腔注射100 mg·kg^-1·d^-1奥马珠单抗；奥马珠单抗+agomir NC组在奥马珠单抗组的基础上尾静脉注射agomir NC；奥马珠单抗+miR-26a-5p agomir组在奥马珠单抗组的基础上尾静脉注射miR-26a-5p agomir。以苏木精-伊红染色法观察肺组织病理变化，以酶联免疫吸附法测定检测炎症因子水平，以实时定量逆转录聚合酶链反应和荧光原位杂交技术检测miR-26a-5p的表达情况，以蛋白质印迹检测焦亡和TLR4/MyD88/NF-κB通路相关蛋白的表达水平。

结果

对照组、模型组、奥马珠单抗组的管壁厚度分别为（35.16±2.95）、（52.94±4.63）和（44.07±3.78）μm，白细胞介素-13（IL-13）水平分别为（18.23±3.94）、（61.84±10.94）和（34.23±6.11）pg·mL^-1，干扰素γ（IFN-γ）水平分别为（68.43±11.59）、（22.94±4.70）和（43.10±8.04）pg·mL^-1，miR-26a-5p mRNA相对表达水平分别为1.00±0.15、2.26±0.31和1.37±0.19。对照组、模型组、奥马珠单抗组、奥马珠单抗+agomir NC组和奥马珠单抗+miR-26a-5p agomir组中NLRP3蛋白相对表达水平分别为1.00±0.11、3.21±0.47、1.77±0.24、1.69±0.27和2.53±0.38，TLR4蛋白相对表达水平分别为1.00±0.13、2.54±0.39、1.86±0.27、1.91±0.30和2.24±0.34，MyD88蛋白相对表达水平分别为1.00±0.15、1.97±0.26、1.44±0.21、1.41±0.18和1.69±0.23，NF-κB蛋白相对表达水平分别为1.00±0.12、2.88±0.37、1.83±0.29、1.77±0.25和2.54±0.41。模型组的上述指标与对照组比较，奥马珠单抗组的上述指标与模型组比较，奥马珠单抗+miR-26a-5p agomir组的上述指标与奥马珠单抗+agomir NC组比较，在统计学上差异均有统计学意义（P<0.05，P<0.01）。

结论

奥马珠单抗可能通过抑制TLR4/MyD88/NF-κB通路的激活来减少NLRP3炎症小体介导的焦亡，从而抑制支气管哮喘大鼠气道重塑，改善大鼠肺功能。

关键词

奥马珠单抗 / 哮喘 / 气道重塑 / Toll样受体4/髓样分化因子88/核转录因子-κB / 核苷酸结合寡聚结构域样受体蛋白3 / 焦亡

Abstract

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Objective

To explore the omalizumab via microRNA (miR)-26a-5p reduced the inflammasome, or the NOD-like receptor themal domain associated protein 3 (NLRP3) mediated pyroptosis on airway remodeling in asthmatic rats, based on the inhibition of the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response protein 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway.

Methods

Fifty SD rats were divided into control group, model group, omalizumab group, omalizumab+agomir NC group and omalizumab+miR-26a-5p agomir group, with 10 rats in each group. The control group was intraperitoneally injected with 0.9% NaCl; the model group established the asthma model; the omalizumab group was intraperitoneally injected with 100 mg·kg^-1·d^-1 omalizumab daily on the basis of model group; the omalizumab + agomir NC group received tail vein injection of agomir NC on the basis of the omalizumab group; the omalizumab+ miR-26a-5p agomir group received tail vein injection of miR-26a-5p agomir on the basis of omalizumab group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of lung tissue; enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory factors; real-time quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and fluorescence in situ hybridization (FISH) were used to detect the expression of miR-26a-5p; Western blotting (WB) was used to detect the pyroptosis and TLR4/MyD88/NF -κB pathway-related proteins expression levels.

Results

The tube wall thickness in control group, model group and omalizumab group were (35.16±2.95), (52.94±4.63) and (44.07±3.78) μm; interleukin-13 (IL-13) levels were (18.23±3.94), (61.84±10.94) and (34.23±6.11) pg·mL^-1; interferon gamma (IFN-γ) levels were (68.43±11.59), (22.94±4.70) and (43.10±8.04) pg·mL^-1; miR-26a-5p mRNA were 1.00±0.15, 2.26±0.31 and 1.37±0.19. The relative expression levels of NLRP3 in control group, the model group, the omalizumab group, the omalizumab +agomir NC group and omalizumab+miR-26a-5p agomir group were 1.00±0.11, 3.21±0.47, 1.77±0.24, 1.69±0.27 and 2.53±0.38; the relative expression levels of TLR4 were 1.00±0.13, 2.54±0.39, 1.86±0.39, 1.90±0.30 and 2.24±0.34; the relative expression levels of MyD88 were 1.00±0.15, 1.97±0.26, 1.44±0.21, 1.41±0.18 and 1.69±0.23; the relative expression levels of NF-κB were 1.00±0.12, 2.88± 0.37, 1.83±0.29, 1.77±0.25 and 2.54±0.41, respectively. The differences of the above indexes were statistically significant when compared the model group with the control group, the omalizumab group with the model group, and the omalizumab+miR-26a-5p agomir group with the omalizumab+agomir NC group (P<0.05, P<0.01).

Conclusion

Omalizumab may reduce NLRP3 inflammasome-mediated pyroptosis by inhibiting the activation of TLR4/MyD88/NF-κB pathway, thus achieving omalizumab inhibited airway remodeling and improved lung function in bronchial asthmatic rats.

Key words

omalizumab / asthmatic / airway-remodeling / Toll-like receptor 4/myeloid differentiation primary response protein 88/nuclear factor kappa-B / NOD-like receptor thermal protein domain associated protein 3 / pyroptosis

引用本文

莫俊俏, 赵桂铃, 焦瀚仪, 孔德志, 张全鹏. 奥马珠单抗通过miR-26a-5p减少炎症小体NLRP3介导的焦亡对哮喘大鼠气道重塑的影响. 中国临床药理学杂志, 2025 , 41 (6) : 816 -821 . DOI: 10.13699/j.cnki.1001-6821.2025.06.013

Jun-qiao MO, Gui-ling ZHAO, Han-yi JIAO, De-zhi KONG, Quan-peng ZHANG. Effects of omalizumab on airway remodeling in asthmatic rats by reducing inflammatory vesicle NLRP3-mediated pyroptosis via miR-26a-5p[J]. Chinese Journal of Clinical Pharmacology, 2025 , 41 (6) : 816 -821 . DOI: 10.13699/j.cnki.1001-6821.2025.06.013

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2025年第41卷第6期

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doi: 10.13699/j.cnki.1001-6821.2025.06.013

接收时间：2024-10-22
首发时间：2026-08-04
出版时间：2025-03-28

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收稿日期：2024-10-22

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作者信息

^1.海南省第五人民医院药剂科，海南海口 570206

^2a.海南医科大学，生理学教研室，海南海口 571199

^2b.海南医科大学，人体解剖学实验室，海南海口 571199

通讯作者:

张全鹏，教授，硕士生导师 MP: 18889790750 E-mail: 510056952@qq.com

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https://castjournals.cast.org.cn/joweb/zglcylxzz/CN/10.13699/j.cnki.1001-6821.2025.06.013

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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