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探讨Aβ亚单位疫苗接种后对Tg2576小鼠脑病理变化和认知退化的预防作用.32只5月龄Tg2576小鼠随机分成4组:对照组(只接种佐剂),Aβ42组(接种Aβ42疫苗),Aβ1~15组(接种Aβ1~15疫苗)和Aβ36~42组(接种Aβ36~42疫苗),每组8只.3组接种疫苗小鼠的血清抗Aβ42抗体滴度比对照组显著增高;脑组织匀浆内也可检测到少量抗体.Morris水迷宫实验结果显示Aβ42组、Aβ1~15组和Aβ36~42组与对照组小鼠的行为学有明显改善.取各组2只小鼠的脾细胞培养,经ConA或各自抗原刺激后,3组疫苗免疫后小鼠脾细胞增殖显著高于对照组;Aβ42组,IL-4和IL-10相对较高,而IL-2和INF-γ相对较低;Aβ1~15组中IL-4和IL-10较高;Aβ36~42组IL-2和INF-γ较高.免疫组织化学法显示对照组小鼠脑皮质与海马部位有大量老年斑,而Aβ42组和Aβ1~15组脑内无老年斑出现,Aβ36~42组小鼠脑内有少量老年斑.实验证明Aβ1~15亚单位疫苗可防止Tg2576小鼠认知行为的退化,阻止Tg2576小鼠脑内Aβ沉积和老年斑的形成.
To investigate the preventive effect of Aβ subunit vaccination on the pathological changes and cognitive decline of Tg2576 mice.Three 25-month-old Tg2576 mice were randomly divided into 4 groups: control group (adjuvant only), Aβ42 group ), Aβ1-15 group (vaccinated with Aβ1-15 vaccine) and Aβ36-42 group (vaccinated with Aβ36-42 vaccine), with 8 mice in each group.The titers of anti-Aβ42 antibody in 3 vaccinated mice were significantly higher than those in control group A small amount of antibodies could also be detected in the homogenate of brain tissue.Morris water maze test results showed that the behavior of Aβ42 group, Aβ1 ~ 15 group and Aβ36 ~ 42 group and the control group were significantly improved. Splenocytes were cultured and stimulated by ConA or their own antigens, the proliferation of spleen cells in three groups of immunized mice was significantly higher than that of the control group; Aβ42 group, IL-4 and IL-10 were relatively high, while IL-2 and INF-γ IL-4 and IL-10 were higher in Aβ1-15 group and higher in Aβ36-42 group than those in Aβ36- 42. Immunohistochemistry showed that a large number of senile plaques were found in the cerebral cortex and hippocampus in control group , While there were no senile plaques in Aβ42 group and Aβ1-15 group, and a small amount of senile plaques in the brain of Aβ36-42 mice.It proved that Aβ1-15 subunit vaccine could prevent Tg2576 mice from cognition Degradation of behavior prevents Aβ deposition and age-related plaque formation in Tg2576 mice.