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目的观察淀粉样前体蛋白/早老素1(APP/PS1)双转基因小鼠海马CA1区神经元胆碱乙酰转移酶(ChAT)表达,评价姜黄素对APP/PS1双转基因小鼠学习记忆的影响。方法将3月龄的APP/PS1双转基因小鼠随机分为模型组、罗格列酮组及姜黄素大、中、小剂量组,并以同月龄遗传背景相同的C57BL/6J小鼠作为正常对照组。各治疗组每天灌胃给药1次,连续灌胃3个月。应用跳台实验、免疫组织化学和蛋白质印迹(Western-blot)检测学习记忆能力和海马神经元ChAT的变化。结果与正常组小鼠相比,模型组小鼠潜伏时间显著缩短(P<0.01),与模型组小鼠相比,姜黄素各剂量组小鼠潜伏时间增加(P<0.05或P<0.01)。免疫组化检测,模型组小鼠海马CA1区ChAT阳性细胞较正常对照组明显减少(P<0.01),而姜黄素干预组可以使其不同程度地恢复。Western blot检测,模型组小鼠海马ChAT的蛋白表达条带比正常组小鼠明显变细、颜色变浅(P<0.01);姜黄素干预组小鼠海马ChAT的蛋白表达条带均明显增粗、颜色加深(P<0.05或P<0.01)。结论姜黄素能通过增加ChAT的蛋白表达,促进阿尔茨海默(AD)模型动物神经传导障碍,进而改善APP/PS1双转基因小鼠的学习记忆能力。
Objective To investigate the expression of choline acetyltransferase (ChAT) in neurons of hippocampus CA1 in amyloid precursor protein / APP1 PS1 transgenic mice and to evaluate the effect of curcumin on learning and memory in APP / PS1 double transgenic mice . Methods Three-month-old APP / PS1 double transgenic mice were randomly divided into model group, rosiglitazone group and curcumin groups (middle and low dose). C57BL / 6J mice with the same genetic background at the same age Control group. Each treatment group administered by gavage once a day, continuous gavage for 3 months. The changes of learning and memory abilities and ChAT of hippocampal neurons were detected by using platform test, immunohistochemistry and Western-blot. Results Compared with the normal group, the latent period of mice in the untreated group was significantly shorter (P <0.01). Compared with the model group, the latency of mice in each dose of curcumin increased (P <0.05 or P <0.01) . Immunohistochemistry showed that the number of ChAT positive cells in hippocampal CA1 region of model group was significantly lower than that of normal control group (P <0.01), while curcumin intervention group could restore it to some extent. Western blot showed that the protein bands of ChAT in hippocampus in model group were significantly thinner and lighter in color than those in normal group (P <0.01). The protein bands of ChAT in hippocampus of curcumin intervention group were significantly thicker , Color deepened (P <0.05 or P <0.01). Conclusion Curcumin can enhance the learning and memory abilities of APP / PS1 double transgenic mice by increasing the protein expression of ChAT and promoting the neurotransmission of Alzheimer’s (AD) model animal.