| 摘要: |
| 目的:研究脂氧素(LX)A4受体激动剂及白介素-1β抗体在Toll样受体2(TLR2)/髓样分化因子88(MyD88)/核因子-κB（NF-κB)信号通路中对哮喘小鼠气道炎症的调控机制。方法:以卵清蛋白(OVA)致敏激发法制备小鼠哮喘模型,60只二级雄性Balb/c小鼠随机分为6组,分别给予脂氧素A4受体激动剂(BML-111)、白介素(IL)-1β抗体、BML-111载体、兔IgG治疗。末次激发后留取血清和肺组织标本,光镜下观察支气管周围炎症浸润情况;测定血清IL-1β、IL-4、IL-8、干扰素(IFN)-γ水平;检测肺组织TLR2、MyD88、NF-κB的表达。结果:OVA致敏的小鼠血清IL-1β、IL-4、IL-8水平升高,IFN-γ浓度降低; OVA致敏导致明显的支气管周围炎症细胞浸润,使支气管炎症分级指数有明显提高;BML-111或IL-1β抗体治疗均能明显阻止上述OVA介导的炎症变化(χ2=28.14，P<0.01)。OVA致敏使肺组织TLR2、MyD88 表达及NF-κB活性升高,BML-111及抗IL-1β抗体可抑制由OVA引发的上述表达变化。结论:OVA可诱导产生气道炎症,这一作用可能受TLR2/MyD88/NF-κB信号通路调控,IL-1β在这一过程中起了至关重要的作用。BML-111和IL-1β抗体可能通过对TLR2/MyD88/NF-κB信号通路的负调控而实现抑制OVA诱发的呼吸道炎症的作用。 |
| 关键词: 哮喘 呼吸道炎症 脂氧素 Toll样受体2 髓样分化因子88 核因子-κB 白介素-1β |
| DOI：doi:10.13407/ j.cnki.jpp.1672-108X.2018.07.001 |
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| 基金项目: |
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| Regulation Effects of Lipoxin A4 Receptor Agonist and Interleukin-1β in Toll-Like Receptors / Mycloid Differentiation Factor 88 / Nuclear Factor-κB Signal Pathway on Asthma Mice with Airway Inflammation |
| Kong Xia1 , Wu Shenghua2 , Zhang Li1 , Cheng Xiaoqing2 |
| (1. Nanjing First Hospital Affiliated to Nanjing Medical University,Jiangsu Nanjing 210006, China; 2. The First Affiliated Hospital of Nanjing Medical University, Jiangsu Nanjing 210029, China) |
| Abstract: |
| Objective: To investigate the regulation effects of lipoxin (LX) A4 receptor agonist and interleukin-1β (IL-1β) antibody in toll-like receptors (TLR2)/mycloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signal pathway on asthma mice with airway inflammation. Methods: Sixty secondary male Balb/c mice with airway inflammation induced by ovalbumin (OVA) immunization were randomly divided into six groups, which were respectively treated with LXA4 receptor agonist, BML-111 and IL-1β antibody, BML-111 vector and rabbit IgG. Serum and lung tissue samples were collected after the last stimulation, and the inflammatory infiltration around the bronchi was observed under light microscope. Serum IL-1β, IL-4, IL-8 and interferon (IFN)-γlevels were measured; the expression of TLR2, MyD88, and NF-κB in lung tissues was determined. Results: OVA sensitization increased the levels of IL-1β, IL-4 and IL-8 in serum, yet the concentration of IFN-γ decreased. OVA sensitization caused significant peribronchial inflammatory cell infiltration and marked increase in bronchial inflammation grading indicators. Treatment of BML-111 or IL-1β antibody can significantly prevent the above-mentioned OVA-mediated inflammatory changes (χ2=28.14，P<0.001). OVA sensitization increased the expression of TLR2 and MyD88 and the activity of NF-κB in lung tissue; these increments induced by OVA were inhibited by treatment of BML-111 and anti-IL-1β antibody. Conclusion: OVA can induce airway inflammation, which may be regulated by TLR2/MyD88/NF-κB signaling pathway; IL-1β plays a pivotal role in the airway inflammation and upregulation of TLR2/MyD88/NF-κB pathway induced by OVA. BML-111 and anti-IL-1βantibody may inhibit airway inflammation induced by OVA through negative regulation of the TLR2/MyD88/NF-κB signaling pathway. |
| Key words: asthma airway inflammation lipoxin toll-like receptor 2 mycloid differentiation factor 88 nuclear factor-κB interleukin-1β |
