西酞普兰对APP23小鼠学习记忆及Aβ神经性病变的影响

发布时间：2018-01-11 05:17

本文关键词：西酞普兰对APP23小鼠学习记忆及Aβ神经性病变的影响　出处：《上海交通大学学报(医学版)》2015年02期 　论文类型：期刊论文

【摘要】：目的探讨早期给予低剂量西酞普兰对阿尔茨海默病(AD)小鼠学习记忆和β淀粉样蛋白(Aβ)病理性变化的影响。方法将5月龄APP23转基因小鼠30只随机分为西酞普兰组和对照组,每组15只。西酞普兰组给予西酞普兰10 mg/kg腹腔注射,对照组腹腔注射等容量的生理盐水,连续3个月。最后一次药物干预后24 h行Morris水迷宫实验,测定小鼠空间学习与记忆能力。水迷宫实验结束后断头取脑,ELISA法检测脑组织中Aβ40和Aβ42水平,免疫组织化学检测老年斑数量,Western blotting检测海马Aβ前体(APP)、β位分解酶1(BACE1)和β-C末端片段(β-CTF)C99/C89的表达水平。结果与对照组比较,西酞普兰组小鼠隐蔽平台逃避潜伏期明显缩短,活动总路径减少,穿越平台次数增加(P0.05);西酞普兰组小鼠脑组织内Aβ40和Aβ42水平明显低于对照组,老年斑数量明显减少(P0.05),但APP、BACE1和β-CTF蛋白表达未见明显改变(P0.05)。结论早期低剂量长疗程给予西酞普兰干预可改善AD小鼠空间学习记忆能力,减轻Aβ神经性病变,其机制可能与西酞普兰上调α分泌酶水平、促进APP在该切割途径代谢增强有关。
[Abstract]:Objective to investigate the effects of low dose citalopram on learning and memory and 尾 -amyloid A 尾 in mice with Alzheimer's disease (AD). Methods Thirty 5-month-old APP23 transgenic mice were randomly divided into citalopram group and control group. 15 rats in each group were given citalopram 10 mg/kg intraperitoneal injection, while the control group received saline of the same volume. The Morris water maze test was performed 24 hours after the last drug intervention for 3 months. The spatial learning and memory abilities of mice were measured. The levels of A 尾 40 and A 尾 42 in brain tissue were detected by ELISA method, and the number of senile plaques was detected by immunohistochemistry. The expression levels of 尾 -CTFU C99 / C89 and 尾 -CTFU C99 / C89 were compared with those in the control group. In citalopram group, the escape latency of covert platform was significantly shortened, the total activity path was decreased, and the frequency of crossing the platform was increased (P0.05). The levels of A 尾 40 and A 尾 42 in the brain tissue of citalopram group were significantly lower than those in the control group, and the number of senile plaques decreased significantly (P 0.05), but APP. The expression of BACE1 and 尾 -CTF protein did not change significantly (P 0.05). Conclusion citalopram can improve the ability of spatial learning and memory in AD mice after early low dose and long course of treatment with citalopram. The mechanism of reducing A 尾 neuropathy may be related to citalopram upregulating 伪 -secretory enzyme level and promoting the metabolism of APP in this pathway.
【作者单位】：重庆医科大学附属儿童医院儿科研究所儿童发育疾病研究教育部重点实验室;重庆医科大学附属儿童医院儿科学重庆市重点实验室;重庆医科大学附属儿童医院重庆市儿童发育重大疾病诊治与预防国际科技合作基地;
【分类号】：R749.16
【正文快照】： 阿尔茨海默病(Alzheimer disease,AD)是最常见的神经退行性疾病,以神经细胞外老年斑沉积、神经元内神经纤维缠结和神经元缺失为主要病理变化。临床表现为隐匿起病,逐渐出现记忆力减退、认知功能障碍、行为异常和社交障碍。病情呈进行性加重,逐渐丧失独立生活能力,发病后10~20

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