嗅三针对阿尔茨海默病小鼠认知功能和海马Aβ、磷酸化JNK、ERK1/2、Tau蛋白表达的影响

Influence of Xiusanzhen on Cognition and Protein Expression of Aβand Phosphorylated JNK,ERK1/2 in Hippocamus of Mice with Alzheimer's Disease

目的探讨嗅三针治疗阿尔茨海默病(AD)小鼠的作用机理。方法 AD动物模型采用APP/PS1双转基因小鼠,随机分为模型组、嗅三针组、嗅神经切断嗅三针组和盐酸多奈哌齐组,正常组和假手术组采用同窝阴性小鼠。嗅三针组和嗅神经切断嗅三针组取印堂穴和双侧迎香穴进行电针治疗,盐酸多奈哌齐组取盐酸多奈哌齐进行灌胃治疗。Y迷宫检测各组小鼠认知功能,免疫组化、Western blot检测小鼠海马内Aβ和p-JNK、p-ERK1/2、p-Tau(Ser 396)蛋白表达情况。结果嗅三针组小鼠认知功能显著改善,有统计学意义(P<0.05);模型组小鼠海马内Aβ和p-JNK、p-ERK1/2、p-Tau(Ser 396)蛋白表达显著高于正常组(P<0.05),经嗅三针和盐酸多奈哌齐治疗后表达显著减少,均具有统计学意义(P<0.05);嗅神经切断嗅三针组治疗后表达无显著变化。结论嗅三针可通过降低AD小鼠海马Aβ和p-JNK、p-ERK1/2、p-Tau(Ser 396)蛋白表达,改善认知功能,而嗅觉通路的完整性是其发挥治疗效果的作用途径。

OBJECTIVE To explore the mechanism of treating Alzheimer＇s disease model mice by Xiusanzhen. METHODS APP/PS1 transgenic mice were taken as AD animal model and randomly divided into model group, Xiusanzhen group, Xiusanzhen with olfactory nerve transected group and Donepezil HCl group, negative mice were taken as control group and sham group. Xiusanzhen group and Xiusanzhen with olfactory nerve transected group had electric acupuncture at Yintang （EX HN3）and Yingxiang （LI20） acupoints. Donepezil HCl group had gastric perfusion with Donepezil HCl.Y maze was used to observe cognitive function of mice. Immunohistochemistry and Western Blot were used to determine the protein expression of Aβ, p-JNK, p-ERK1/2, p-Tau （Ser 396） in hippocampus of mice. RESULTS Xiusanzhen group significantly improved cognitive function（ P 〈 0.05 ）; protein expression of Aβ, p-JNK, p-ERK1/2, p-Tau （Ser 396） protein in the model group was significantly higher than the others, while significantly reduced after Xiusanzhen and Donepezil HCl treatment; however, was no significant change and statistical significance after Xiusanzhen with olfactory nerve transected treatment （ P 〉0.05）. CONCLUSION Xiusanzhen can regulate protein expression of Aβ, p-JNK, p-ERK1/2, p-Tau （Ser 396） and improve the cognitive function of AD mice, meanwhile, the integrity of the olfactory pathway is the way to play the theraputic effect.