高压氧对Aβ25—35诱导大鼠认知和记忆障碍及其海马神经元凋亡的影响  

A possible anti-apoptosis mechanism of hyperbaric oxygen in rats with memory impairments induced by Aβ25-35

作　　者：田小强[1] 张丽[2] 杨琳[3] 黄平[4] 钱霞[4] 黄培林[3] 张丽达[4] 

机构地区：[1]东南大学附属第二医院肿瘤内科,南京210009 [2]南京医科大学附属脑科医院老年科 [3]东南大学医学院病理学系 [4]东南大学附属中大医院高压氧科

出　　处：《中华物理医学与康复杂志》2014年第1期7-11,共5页Chinese Journal of Physical Medicine and Rehabilitation

基　　金：南京市社会发展科技计划（200804039）;南京市医学科技发展重点项目资助（ZKX13034）

摘　　要：目的探讨高压氧（HBO）治疗对β-淀粉样蛋白（Aβ）25—35所致拟阿尔茨海默病（AD）模型大鼠认知和记忆功能的改变及其海马神经元凋亡情况的影响。方法选取健康成年雄性SpragueDawley（SD）大鼠48只，按随机数字表法分为正常对照组、假手术组、模型组和HBO治疗组，每组12只。正常对照组不做任何处理。其余各组大鼠给予10％水合氯醛（4m1）腹腔注射麻醉，假手术组大鼠每侧海马注射5μl生理盐水；造模大鼠（模型组和HBO治疗组）每侧海马注射5μl的A325—35制备拟AD大鼠痴呆模型。造模成功后，模型组大鼠不做任何治疗处理；HBO治疗组大鼠造模2周后，常规HBO治疗，每日1次，10d为1个疗程，中间休息3d，共2个疗程。采用Morris水迷宫法观察各组大鼠空间记忆能力的改变，TUNEL染色观察大鼠海马神经元凋亡情况的改变，同时检测海马组织凋亡相关基因Bcl-2和Bax的mRNA、蛋白表达的改变。结果水迷宫实验中，第5天和第6天HBO治疗组大鼠的逃避潜伏期与模型组比较显著缩短（33．4±4．5）s比（48．1±2．7）s，（20．8±1．7）s比（40．5±1．9）S，P〈0．05，空间探索实验中HBO治疗组大鼠在原平台所在象限的时间及穿过原平台的次数较模型组显著增加（35．8±5．6）％比（21．1±3．8）％，（4．8±1．1）次比（3．1±1．2）次，P〈0．05。TUNEL染色中，模型组海马神经元中胞核呈现棕色凋亡形态的较多，而HBO治疗组则见少数凋亡的海马神经元。海马组织凋亡基因检测中，HBO治疗组Bcl-2mRNA和蛋白的表达显著高于模型组（P〈0．05），其BaxmRNA和蛋白的表达则相应地降低。结论HBO可能通过抑制Aβ25—35诱导的海马神经元凋亡而改善AD大鼠模型的认知和记忆能力。Objective To explore the possible protective effect of hyperbaric oxygen （HBO） on cogni- tive deficits induced by amyloid β25-35 （ Aβ25-35 ） and neuronal apoptosis in the hippocampi of rats with Alzheimer＇s disease （AD）. Methods The animal AD model was established in 24 Sprague-Dawley rats by bilateral hippocampal injection of Aβ25-35. Twelve rats were injected with normal saline as controls, and anoth- er 12 served as normal controls. After the injection, the model rats were further divided into a model group and a treatment group. All the rats were housed with normal feeding for 2 weeks and then those in the treatment groups received a total of 2 courses of HBO treatment （ 10 days each with an interval of 3 days in between）. The other groups were left with no treatment. After the treatment, the rats＇ learning and memory ability were tested u- sing Morris＇ water maze test, and any neuronal changes were observed using TUNEL staining. The expression of mRNA and Bcl-2 and Bax proteins in the hippocampus were detected using a RT-PCR and Western blotting. Results HBO significantly improved the learning and memory impairment and alleviated neuronal apoptosis in the hippocampus compared against the control group. In addition, HBO treatment significantly increased the mRNA and protein expression of Bcl-2 and down-regulated the expression of Bax. Conclusion HBO treatment can prevent learning and memory impairment induced by Aβ25-35 peptides, which might be mediated by inhibi- ting neuronal apoptosis in the hippocampus.

关 键 词：阿尔茨海默氏病 高压氧 Β-淀粉样蛋白 细胞凋亡 

分 类 号：R459.6[医药卫生—治疗学]