脂氧素A4受体激动剂及白介素-1β在Toll样受体2/髓样分化因子88/核因子-κB信号通路对哮喘小鼠气道炎症的调控作用  

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

作　　者：孔霞[1] 吴升华[2] 张莉[1] 陈筱青[2] Kong Xia;Wu Shenghua;Zhang Li;Cheng Xiaoqing(Nanfing First Hospital Affiliated to Nanjing Medical University, Jiangsu Nanjing 210006, China;The First Affiliated Hospital of Nanjing Medical University, Jiangsu Nanjing 210029, China)

机构地区：[1]南京医科大学附属南京医院(南京市第一医院),江苏南京210006 [2]南京医科大学第一附属医院,江苏南京210029

出　　处：《儿科药学杂志》2018年第7期1-6,共6页Journal of Pediatric Pharmacy

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(My D88)/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Ig G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、My D88、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、My D88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/My D88/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/My D88/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。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（ My D88）/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-1βantibody,BML-111 vector and rabbit Ig G. 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）-γ levels were measured; the expression of TLR2,My D88,and NF-κB in lung tissue 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. 01）. OVA sensitization increased the expression of TLR2 and My D88 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/My D88/NF-κB signaling pathway; IL-1β plays a pivotal role in the airway inflammation and upregulation of TLR2/My D88/NF-κB pathway induced by OVA. BML-111 and anti-IL-1β antibody may inhibit airway inflammation induced by OVA through negative regulation of the TLR2/My D88/NF-κB signaling pathway.

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 

分 类 号：R725.6[医药卫生—儿科]