白术内酯Ⅲ对痴呆大鼠学习记忆能力及海马Bcl-2表达的影响

Effects of Atractylenolide Ⅲ on learning and memory impairment and Bcl-2 expression in hippocampus in a rat model of Alzheimer's disease

采用大鼠双侧侧脑室注射Aβ1-42建立老年痴呆动物模型,通过Morris水迷宫行为实验、海马乙酰胆碱酯酶(AChE)活性生化测定及海马凋亡抑制基因Bcl-2表达Western Blot检测,研究了白术内酯Ⅲ(AtractylenolideⅢ,ATLⅢ)对痴呆大鼠学习记忆能力的影响.结果表明:与模型组相比,ATLⅢ中、高剂量组的逃避潜伏期显著缩短(P<0.01),在原平台象限的停留时间显著延长(P<0.01),海马AChE活性显著降低(P<0.05),Bcl-2表达显著增高(P<0.05,P<0.01).结果提示白术内酯Ⅲ可显著改善痴呆大鼠的学习记忆能力,其机制可能与抑制AChE活性及上调海马Bcl-2基因的表达有关.本研究对于神经保护作用药物的开发具有重要的临床意义.

Animal models of Alzheimer’s disease were established by injection of Aβ1-42 into the bilateral cerebral ventricle of rats.Through the Morris water maze behavior test,hippocampal acetylcholinesterase（AChE）biochemical assay and Western Blot detection of Bcl-2 expression in hippocampus,to study the effect of AtractylenolideⅢ（ATLⅢ）on learning and memory in dementia rats.The results showed that in the water maze test,the escape latency of the model group was significantly longer than that of the control group（P〈0.01）,and the retention time in the original platform quadrant was significantly shorter than that of the control group（P〈0.01）.The escape latency of middle and high dose of ATLⅢwas significantly shorter than that of the model group（P〈0.01）,and the retention time in the original platform quadrant was significantly longer than that of the model group（P〈0.01）.The activity of AChE in hippocampus in model group was significantly higher than that in control group（P〈0.05）,and the medium and high dose ATLⅢ group was significantly lower than the model group（P〈0.05）.The expression of Bcl-2 in hippocampus in model group was significantly lower than that in control group（P〈0.01）,and the medium and high dose ATLⅢ group was significantly higher than the model group（P〈0.05,P〈0.01）.The results suggest that ATLⅢcan significantly improve learning and memory in dementia rats,it may be related to the inhibition of AChE activity and up-regulation of Bcl-2 expression in hippocampus.This study has important clinical implication for the development of neuroprotective drugs.