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- 2017
CaMKII反义寡核苷酸对阿尔茨海默病样大鼠海马细胞损伤的保护作用及其机制
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Abstract:
摘要：目的 研究CaMKII反义寡核苷酸对阿尔茨海默病(Alzheimer’s disease, AD)样大鼠海马细胞损伤的保护作用及其机制。方法 采用Aβ1-40和AlCl3双干预法建立AD样大鼠模型；造模成功的大鼠随机分为AD模型组(AD)、溶剂对照组(TE)、反义寡核苷酸组(AS)和错义寡核苷酸组(MS)；以Morris水迷宫观察大鼠逃避潜伏期，用TUNEL染色检测大鼠海马细胞损伤情况；免疫印迹法检测CaMKII、NR1和NR2B在大鼠海马的表达变化。结果 AS组大鼠Morris水迷宫逃避潜伏期显著缩短，海马细胞损伤明显减轻，海马CaMKII、NR1和NR2B的表达显著减少；与AD组、TE组或MS组相比，差异均具有统计学意义(P<0.05)。结论 CaMKII反义寡核苷酸能够通过改善AD样大鼠学习记忆能力和减轻AD样大鼠海马细胞损伤而发挥神经保护作用，且这种神经保护作用与其降低CaMKII、NR1和NR2B的病理性高表达有关。
ABSTRACT: Objective?? To study the protective effects of CaMKII antisense oligonucleotide on cell injury of rat hippocampus induced by Alzheimer’s disease (AD) and its mechanism. Methods?? AD-like rat model was established by Aβ1-40 and AlCl3 intervention method. The model rats were then randomly divided into AD model group (AD), solvent control group (TE), CaMKII antisense oligonucleotide group (AS), and CaMKII missense oligonucleotide group (MS). The escape latency of the rats was observed by Morris water maze; the damage of hippocampal cells was detected by HE staining and TUNEL staining. The changes of CaMKII, NR1 and NR2B expressions in rat hippocampus were detected by Western blot. Results?? Compared with those in AD group, TE group and MS group the escape latency of rats was significantly shorter, the hippocampal neurons damage significantly reduced and CaMKII, NR1 and NR2B protein expressions were significantly decreased in CaMKII antisense oligonucleotide group (P<0.05). Conclusion?? CaMKII antisense oligonucleotide plays a neuroprotective role by reducing the AD-like rat hippocampus cell damage and improve learning and memory ability, which may be related to the pathologically high expressions of CaMKII, NR1 and NR2B
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