阻断Notch信号对疫苗增强性免疫病理的作用

发布时间：2018-07-29 15:26

【摘要】：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(P0.05),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(P0.05),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(P0.05)。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。
[Abstract]:Objective to investigate the regulatory effect of blocking Notch signal on enhanced immunopathology of FI-RSV vaccine. Methods the FI-RSV vaccine with adjuvant Al (OH) _ 3 was prepared and immunized with C57BL/6 mice twice, then the body weight of each group was detected, and lung tissue sections, staining and cytokine transcriptional expression were detected. Results there was no significant difference in serum IgG antibody levels before immunization, significant weight loss in FI-RSV Al (OH) group after immunization, and significant mucus secretion in FI-RSV Al (OH) 3 and FI-RSV Al (OH) 3 L-685458 groups by PAS staining in pathological sections. The HE staining of pathological sections showed that a large number of inflammatory cells were infiltrated in the lungs of FI-RSV Al (OH) 3 and FI-RSV Al (OH) 3 L-685458 groups. The inflammatory response of FI-RSV Al (OH) group is inclined to the alveolar wall FI-RSV Al (OH) subgroup 3 L-685458. The expression of RSV-N gene in the lung tissue of the three groups is similar to that of the FI-RSV Al (OH) 3-L-685458 group (P0.05). The expression of IFN- 纬 -TNF- 伪 -betbetIL-17ROR- 纬 t in the FI-RSV Al (OH) group 3 is not significantly different from that in the FI-RSV Al (OH) 3-L-685458 group. The expression of IL-4, IL-5 and GATA-3 was significantly higher in the other two groups than in the other two groups (P0.05). The expression of IL-4, IL-5 and GATA-3 was significantly higher in the 3L-685458 group than that in the other two groups (P0.05). Conclusion compared with L-685458, Al (OH) _ 3 alone can induce the dominant response of Th1 and Th17 type, and the predominant response of Th2 type after blocking alveolar wall response, and the inflammatory response of tracheal wall and perivascular reaction is stronger than that of L-685458 as adjuvant.
【作者单位】：邢台医学高等专科学校;河北医科大学免疫学教研室;
【基金】：河北省自然科学基金项目(No.H2016206473)
【分类号】：R392-33

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