当归多糖对阿尔茨海默病模型大鼠海马神经元内质网应激的影响

目的:探讨当归多糖对阿尔茨海默病(Alzheimer Disease,AD)大鼠学习记忆能力、海马组织形态以及内质网应激(Endoplasmic Reticulum Stress,ERS)相关因子葡萄糖调节蛋白78(Glucose Regulating Protein 78,GRP78)、基因转录调节因子CCAAT增强子结合蛋白的同源蛋白(C/EBP Homologous Protein,CHOP)、半胱氨酸天冬氨酸蛋白酶12(Cysteine Aspartate Protease-12,Caspase-12)的影响。方法:70只大鼠进行水迷宫实验学习记忆能力筛选,去除不合格大鼠。将筛选合格大鼠随机分为假手术组、模型组、阳性对照组、当归多糖低剂量组、当归多糖中剂量组、当归多糖高剂量组,每组10只。模型组及药物干预组大鼠双侧海马区定向注射β-淀粉样蛋白(Aβ25-35)复制阿尔茨海默模型,假手术组定向注射生理盐水。5 d后进行水迷宫实验观察大鼠学习记忆能力。连续灌胃28 d,假手术组和模型组均给予生理盐水,其他药物干预组均给予相应药液。末次给药后再次进行水迷宫实验观察大鼠学习记忆能力。取材观察海马及大脑皮质形态学变化以及检测GRP78、CHOP、Caspase-12蛋白的表达。结果:与假手术组比较,模型组大鼠逃避潜伏期延长,穿越原平台次数减少,海马GRP78、CHOP以及Caspase-12蛋白的表达上升,差异均有统计学意义(P<0.05),HE染色可见海马区神经元细胞损伤;与模型组比较当归多糖各组可不同程度缩短阿尔茨海默大鼠逃避潜伏期,增加穿越原平台次数,同时可抑制海马GRP78、CHOP以及Caspase-12蛋白的表达,差异均有统计学意义(P<0.05),HE染色可见海马区神经元细胞损伤减轻。结论:当归多糖可能通过抑制内质网应激,减少神经细胞凋亡,提高大鼠学习记忆能力,从而在阿尔茨海默病理过程中发挥保护作用。

The effects of angelica polysaccharide on hippocampal neuronal endoplasmic reticulum stress in model rats with Alzheimer disease

Objective:To discuss the effects of angellica polysaccharide on learning and memery abilities,hippocampus organizational shape and GRP78,CHOP,Caspase-12 of endoplasmic reticulum stress-related factors in Alzheimer disease rats.Methods:70 SPF Wistar rats were selected for learning and memory ability screening by Morris water maze experiment.The unqualified rats were removed.The qualified rats were succefully randomzied into the sham-operation group,the model group,the positive group,the low-dose group,the medium-dose group,and the high-dose group,with 10 rats in each group.The rats in the model group and medication groups were injected with Aβ25-35 by stereotatic techniques to reproduce Alzheimer models,the rats in the sham-operation were injected with normal saline.In 5 days,water maze experiments were conducted to observe the learning and memory capacity of rats after the operation.Gavage was continued for 28 days.Rats in the sham-operation group and the model group were given normal saline,while rats in the other medication groups were given corresponding liquid medicine.The learning and memory ability of rats in each group was tested again by Morris water maze experiment after last gavage.The morphological changes of hippocampus and cerebral cortex were observed.The contents of GRP78,CHOP and Caspase-12 protein in hippocampus were determined.Results:Compared with the sham-operation group,escape latency of the rats in the model group was longer,the number of crossing the original platform was reduced,and the protein expression level of GRP78,CHOP and Caspase-12 in hippocampal was increased,which was with statistically significant difference(P<0.05).The damage of hippocampus neurons cells was observed with HE stain.Compared with the model group,the escape latency in each medication group was shortened in different degrees,the number of crossing the original platform was increased,and the protein expression level of GRP78,CHOP and Caspase-12 in hippocampal were decreased,which was with statistically significant difference(P<0.05).HE staining showed that the damage of hippocampus neurons cells was reduced.Conclusion:Angellica polysaccharide may reduce neuronal apoptosis and improve learning and memory of rats through restraining the endoplasmic reticulum stress,so as to play a preventive role in the pathological process of Alzheimer disease.