Aβ3-10基因疫苗对幼年鼠脑内老年斑沉积及记忆障碍预防作用的研究

发布时间：2018-03-30 08:59

本文选题：阿尔茨海默病　切入点：免疫治疗　出处：《中风与神经疾病杂志》2017年07期

【摘要】：目的构建表达重复10次的Aβ3-10肽段的DNA疫苗,并探讨其对幼年APP/PS1转基因鼠脑内Aβ沉积的预防及对其延迟记忆障碍的作用。方法将该疫苗用体外电穿孔的方法肌肉免疫3月龄的APP/PS1双转基因鼠,并分别做行为学、Aβ抗体、脾细胞培养上清细胞因子、脑内Aβ沉积及星型胶质细胞测定。结果 p(Aβ3-10)10-MT和Aβ42组免疫一次后即产生抗体,并随着免疫次数增多而增加,类型主要为IgG1,IgG1/IgG2a明显高于Aβ42组。在Morris水迷宫中,p(Aβ3-10)10-MT和Aβ42组潜伏期明显减短,空间探索实验在平台象限所在时间均较pc DNA3.1组长。p(Aβ3-10)10-MT和Aβ42组脾细胞培养上清IL-4和IFN-γ均增高,而在p(Aβ3-10)10-MT组,IL-4较高,IFN-γ较低。免疫组化结果提示皮质和海马区老年斑沉积减少。结论 DNA疫苗p(Aβ3-10)10-MT免疫幼年APP/PS1双转基因鼠后能产生高滴度的抗体,免疫反应为Th2型,预防脑内Aβ的聚集的同时延缓了记忆障碍的发生与发展,避免了副反应的发生,有待成为预防阿尔茨海默病的有效疫苗。
[Abstract]:Objective to construct a DNA vaccine expressing A 尾 3-10 peptide fragment for 10 times. To investigate the prevention of A 尾 deposition in the brain of juvenile APP/PS1 transgenic mice and its effect on delayed memory impairment. Methods the vaccine was immunized intramuscularly with 3-month-old APP/PS1 double transgenic mice by electroporation in vitro, and the behavioral A 尾 antibody was used respectively. The supernatant cytokines of splenocyte culture, A 尾 deposition in brain and astrocytes were measured. Results the antibody was produced in group A 尾 3-10)10-MT and A 尾 42, and increased with the increase of immunization times. In the Morris water maze, the latencies of A 尾 3-10)10-MT and A 尾 42 groups were significantly reduced, and the IL-4 and IFN- 纬 of splenocyte culture supernatant of PC DNA3.1 group and A 尾 42 group were significantly higher than those of PC DNA3.1 group and A 尾 42 group. The results of immunohistochemistry indicated that the deposition of senile plaque in cortex and hippocampus decreased. Conclusion DNA vaccine Pa 尾 3-10)10-MT can produce high titer antibody after immunizing juvenile APP/PS1 double transgenic mice, and the immunoreaction is Th2 type. Preventing the accumulation of A 尾 in the brain at the same time retarding the occurrence and development of memory disorder, avoiding the occurrence of side effects, waiting to become an effective vaccine for the prevention of Alzheimer's disease.
【作者单位】：中国医科大学附属第一医院老年医学科;中国医科大学附属第一医院皮肤科;中国医科大学附属第一医院神经内科;
【基金】：国家自然基金面上项目(No.81371227) 国家自然科学基金项目(No.81602741) 辽宁省科技厅博士启动基金(No.201501013) 中国医科大学校内科研基金新教师基金项目(No.XZR20160006)
【分类号】：R749.16

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