中国神经再生研究(英文版) ›› 2014, Vol. 9 ›› Issue (8): 872-877.doi: 10.4103/1673-5374.131605

• 原著:退行性病与再生 • 上一篇    下一篇

鼻粘膜吸入淀粉样β肽3-10s腺缺陷病毒:可降低Aβ1-42引起的细胞毒性

  

  • 收稿日期:2014-02-25 出版日期:2014-04-25 发布日期:2014-04-25
  • 基金资助:

    国家自然科学基金(No.30471927)

Nasal mucosal inhalation of amyloid-beta peptide 3–10 defective adenovirus attenuates cytotoxicity induced by beta-amyloid (1–42)

Tongzi Jiang, Wanshu Guo, Sha Sha, Xiaona Xing, Rong Guo, Yunpeng Cao   

  1. Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Received:2014-02-25 Online:2014-04-25 Published:2014-04-25
  • Contact: Yunpeng Cao, Ph.D., Department of Neurology, First Affiliated Hospital of China Medical University, Shenyang 110005, Liaoning Province, China
  • Supported by:

    This study was supported by the National Natural Science Foundation of China, No. 30471927.

摘要:

给予3月龄阿尔茨海默病转基因小鼠Aβ1-42,Plp-Adeno-X-CMV-(Aβ3-10)10-CpG [AdCpG-(Aβ3-10)10]或AdCpG病毒液经鼻黏膜吸入进行免疫。LISA检测发现随着免疫次数的增加,给予Aβ1-42和AdCpG-(Aβ3-10)10的小鼠血清Aβ42抗体滴度明显增高。在刀豆球蛋白A及AdCpG-(Aβ3-10)10刺激下,Aβ1-42和AdCpG-(Aβ3-10)10免疫小鼠脾细胞增殖数量明显增多。同时AdCpG-(Aβ3-10)10免疫的小鼠脾细胞培养液中白细胞介素4,10含量较高,白细胞介素2、干扰素γ含量较低;单纯Aβ1-42免疫的小鼠脾细胞培养液中白细胞介素2,4,10和干扰素γ含量均较高。说明AdCpG-(Aβ3-10)10疫苗在产生抗Aβ42抗体的基础上,产生了强烈的体液免疫反应,而细胞免疫应答较弱,避免了Aβ1-42引起的细胞毒性。

关键词: 神经再生, 神经退行性疾病, 阿尔茨海默病, 免疫治疗, 淀粉样β肽疫苗, 细胞因子, 体液免疫, 炎症反应, NSFC grant

Abstract:

Three-month-old Alzheimer’s disease model transgenic mice were immunized with Aβ1–42, Plp-Adenovirus [Ad]-X-CMV-(Aβ3–10)10-CpG [AdCpG-(Aβ3–10)10] or AdCpG virus fluid via nasal mucosal inhalation, respectively. ELISA analysis of serum showed Aβ42 antibody titers were significantly increased in mice immunized with Aβ1–42 and AdCpG-(Aβ3–10)10. Concanavalin A and AdCpG-(Aβ3–10)10 stimulation significantly increased the number of proliferating spleen cells cultured from AdCpG(Aβ3–10)10 and Aβ42 groups compared with the control group. In the AdCpG(Aβ3–10)10 group, levels of interleukin (IL)-4 and IL-10 were increased, while those of IL-2 and interferon-γ were decreased. In the Aβ42 group, levels of IL-4, IL-10, IL-2 and interferon-γ were all increased. Experimental findings indicate that AdCpG-(Aβ3–10)10 vaccine can produce strong T helper 2 (Th2) humoral immune responses in addition to the production of Aβ42 antibody. The cellular immunologic response was weak and avoided Aβ1–42-mediated cytotoxicity.