鹿茸多肽对APP/PS1双转基因小鼠Rho/ROCK通路的影响

目的 探讨鹿茸多肽(VAP)对APP/PS1双转基因小鼠Rho/ROCK通路的影响.方法 APP/PS1双转基因小鼠随机分为模型组和鹿茸多肽组,每组20只,另以同窝同性别阴性小鼠20只设立为对照组.鹿茸多肽组小鼠鹿茸多肽100 mg/kg灌胃给药,每天1次,连续28 d.治疗后水迷宫实验检测并记录小鼠逃避潜伏期和穿越平...

Effects of velvet antler polypeptide on Rho/ROCK pathway in APP/PS1 double transgenic mice

Objective To study the effect of velvet antler polypeptides (VAP) on Rho/ROCK pathway in APP/PS1 double transgenic mice. Methods APP/PS1 double transgenic mice were randomly divided into model group and velvet antler polypeptide group, 20 mice in each group, and control group consisting of 20 mice of the same litter and the same gender negative. The mice in VAP group were given velvet antler polypeptide 100 mg/kg by intragastric administration once a day for 28 days. After treatment, the water maze experiment was detected and recorded the escape latency and the number of crossing platforms of the mice; the ultrastructures of the synapse were observed by transmission electron microscopy; the expression of Rhs homolog gene family member A(RhoA) and Rho associated coiled-coil forming protein kinase Ⅱ(ROCKⅡ) in the hippocampal CA1 area were observed by immunofluorescence. The expression levels of RhoA and ROCKⅡ protein in the hippocampus were detected by Western blotting. The contents of hippocampus amyloid β-protein(Aβ)1-42 were determined by ELISA. Results Compared with the model group, the escape latency was shortened, and the numbers of crossing platforms was increased in control group and VAP group. Compared with the model group, the synapse count in the hippocampus was increased, the width of the synaptic gap was decreased, and the thickness of the post-synaptic compact was increased in the control group and VAP group, the difference had significant(P＜0.05). Compared with the model group, the expression levels of RhoA and ROCKⅡ in CA1 area reduced in control group and VAP group, and the expression levels of RhoA and ROCKⅡ protein in the hippocampus also reduced in control group and VAP group by Western blotting (P＜0-05).Compared with the model group, the contents of hippocampal Aβ1-42 in the control group and VAP group decreased. Conclusion Velvet antler polypeptide has a protective effect on nerve damage in Alzheimer’s disease model mice, and its mechanism may promote the changes of synaptic structure and reduction of Aβ1-42 content, reduce nerve damage and improve cognitive function by inhibiting the expression of RhoA and ROCKⅡ in Rho/ROCK pathway.