新生期接种乙肝疫苗联合丰富环境对小鼠神经发生及行为的影响

Effects of hepatitis B vaccine combined with enriched environment on neurogenesis and behavior in mice

目的探究新生期接种乙肝疫苗联合丰富环境对小鼠神经发生及行为的影响,为其更深入的机制研究奠定基础。方法新生小鼠均等的随机分为两组,其中半数小鼠出生24 h内腹腔注射乙肝疫苗(100μg/m L),于出生后第1、3周分别加强免疫一次,其余注射无菌PBS作对照。待出生后第4周,子代小鼠再次被均等的随机分为两组,分别为丰富环境组和普通环境组。利用水迷宫实验检测小鼠海马依赖型的学习记忆能力;免疫荧光技术检测小鼠海马的神经发生;ELISA方法检测小鼠血清中的IL-4、IFN-γ以及海马中的BDNF含量。结果乙肝疫苗联合丰富环境组小鼠的学习记忆能力、神经发生及海马的BDNF水平高于乙肝疫苗组小鼠,差异具有统计学意义(P<0.05),但与对照组小鼠相比无显著差异(P>0.05);联合组小鼠血清中的IFN-γ/IL-4比值较乙肝疫苗组小鼠明显升高,差异具有统计学意义(P<0.05),与对照组小鼠相比并无显著差异(P>0.05)。结论新生期接种乙肝疫苗损害小鼠的神经发生和海马依赖型的学习记忆能力,并使得小鼠Th1/Th2平衡向Th2偏移,青春期进行丰富环境干预后可使其恢复到与对照组相近的水平。

Objective To explore the effect of hepatitis B vaccine combined with enriched environment on neurogenesis and behavior in mice. Methods The neonatal mice were equally randomized into two groups, half of the mice received intraperitoneal injection of hepatitis B vaccine within 24 hours （100 μg/mL）. Mice immunized with HBV at PW0 and received two boost inocula- tions with HBV at PW1 and PW3. The other mice were injected intraperitoneally with PBS as control. Fourth weeks after birth, offspring mice were equally randomly divided into two groups, namely, enriched environment group and general environment group. Learning and memory function was tested by Morris water maze. Neurogenesis was measured by immunofluorescence. ELSA was performed to detect levels of IFN-γand IL-4 in serum and hippoeampal BDNF level. Results Hepatitis B vaccine combined with enriched environment group learning and memory ability of mice, neurogenesis in hippocampus and BDNF is higher than the level of hepatitis B vaccine in mice, the difference was statistically significant （P〈O.05） , but compared to the control mice had no signifi- cant difference （P〉0.05）. The ratio of IFN-γ/IL-4 in the serum of the combined group was significantly higher than that of the hepa- titis B vaccine group, the difference was statistically significant （P〈0.05） , and there was no significant difference compared with the control group （P〉0.05）. Conclusion Inoculation with hepatitis B vaccine in the neonatal stage impaired neurogenesis and hippocampal dependent learning and memory in mice, and the balance of Thl/Th2 in mice is shifted to Th2, adolescent rich environmental treatment can restore it to the control level.