摘要
Abstract
Objective To explore the omalizumab via microRNA(miR)-26 a-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.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分类
药学
