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目的探讨阻断Notch信号对FI-RSV疫苗增强性免疫病理的调节作用。方法制备加入佐剂Al(OH)3的FI-RSV疫苗,肌注免疫C57BL/6小鼠2次,检测抗体;攻毒后,检测各组体重变化,并作肺组织切片及染色检查和细胞因子转录表达检测。结果免疫前各组血清IgG抗体水平无显著差异;免疫后,FI-RSV+Al(OH)_3组体重下降显著;病理切片PAS染色显示FI-RSV+Al(OH)_3和FI-RSV+Al(OH)_3+L-685,458组的粘液分泌均较明显,病理切片HE染色显示FI-RSV+Al(OH)_3和FI-RSV+Al(OH)_3+L-685,458组肺部均显示大量炎症细胞浸润,炎症反应较强,FI-RSV+Al(OH)_3组炎症反应倾向于肺泡壁,FI-RSV+Al(OH)_3+L-685,458组炎症反应倾向于气管壁和血管周;FIRSV+Al(OH)_3组肺组织RSV-N基因的表达量与FI-RSV+Al(OH)_3+L-685,458组比较差异无统计学意义(P>0.05),FI-RSV+Al(OH)_3组的IFN-γ、TNF-α、T-bet、IL-17、ROR-γt基因的表达量显著高于其他两组(P<0.05),FIRSV+Al(OH)_3+L-685,458组IL-4、IL-5、GATA-3基因的表达量显著高于其他两组(P<0.05)。结论 Al(OH)_3单独作为佐剂比添加L-685,458诱发Th1及Th17型优势应答和以肺泡壁反应为主的炎症反应强;Notch信号阻断后诱发的Th2型优势应答及以气管壁和血管周反应的炎症反应更强。
Objective To investigate the role of blockade of Notch signaling in enhancing the immunopathology of FI-RSV vaccines. Methods FI-RSV vaccine with adjuvant Al (OH) 3 was prepared and intramuscularly immunized C57BL / 6 mice twice to detect the antibody. After challenge, the body weight of each group was measured and the lung tissue sections were stained and examined for staining and cells Factor Transcriptional Expression Detection. Results There was no significant difference in the level of serum IgG before immunization. The body weight of FI-RSV + Al (OH) 3 group decreased significantly after immunization. The pathological changes of FI-RSV + Al (OH) 3 and FI- (OH) _3 + L-685,458 group were more obvious mucus secretion, pathological sections HE staining showed FI-RSV + Al (OH) _3 and FI-RSV + Al (OH) _3 + L-685,458 group showed a large number of lung Inflammatory cells infiltrated and inflammatory reaction was stronger. Inflammatory reaction in FI-RSV + Al (OH) 3 group tended to alveolar wall. Inflammatory reaction in FI-RSV + Al (OH) There were no significant differences in the expression of RSV-N gene between FI-RSV + Al (OH) 3 + L-685,458 group and FI-RSV + Al (OH) OH) _3 group, the expression of IFN-γ, TNF-α, T-bet, IL-17 and ROR-γt were significantly higher than those in the other two groups (P < The expression of IL-4, IL-5 and GATA-3 in 685,458 group was significantly higher than the other two groups (P <0.05). Conclusion Al (OH) _3 alone adjuvant than L-685,458 induced Th1 and Th17-type predominant response and inflammatory response to alveolar wall reaction predominant; Th2 type predominant response induced by Notch signaling blockade and to the tracheal wall and Inflammatory reaction of the perivascular response is stronger.