当归补血汤对血管性痴呆大鼠学习记忆障碍改善及其机制研究

Effect and Mechanism of Danggui Buxue Decoction on Learning and Memory Impairment in Rats with Vascular Dementia

目的:研究当归补血汤对血管性痴呆大鼠学习记忆、抗氧化作用和对胆碱能神经递质的影响。方法:Wistar大鼠随机分为模型对照组、吡拉西坦0.324 g/kg组、当归补血汤36、54 g/kg组,另设假手术对照组,灌胃给予相应药物或生理盐水,连续30 d。Morris水迷宫进行定位航行和空间搜索实验;测定大鼠大脑皮层和海马组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活力、丙二醛(MDA)、乙酰胆碱(Ach)和乙酰胆碱酯酶活性(AchE)活力或含量,HE染色观察大脑海马区结构变化情况。结果:Morris水迷宫定位航行行为学检测和空间搜索实验中,与正常对照组比较,模型对照组第5 d逃避潜伏期显著升高(P<0.01),逃逸平台滞留时间、有效区域运动时间及逃逸平台进入次数显著降低(P<0.01);与模型对照组比较,各药物组第5 d逃避潜伏期均显著降低(P<0.01),逃逸平台滞留时间、有效区域运动时间及逃逸平台进入次数显著升高(P<0.01)。与正常对照组比较,模型对照组大脑皮质MDA含量显著升高(P<0.01),大脑皮质GSH-PX和SOD活性明显降低(P<0.05或P<0.01),大脑海马Ach含量显著降低(P<0.01),AchE活性显著升高(P<0.01);与模型对照组比较,各药物组MDA含量均显著降低(P<0.01),GSH-PX和SOD活性显著升高(P<0.01),大脑海马Ach含量显著升高(P<0.01);除吡拉西坦0.324 g/kg组外,当归补血汤36、54 g/kg组AchE活性显著降低(P<0.01),各给药组大鼠海马区病理变化明显改善。结论:当归补血汤可通过提高抗氧化酶活性和促进胆碱能神经递质的释放,抑制AchE活性,改善大鼠学习记忆能力治疗血管性痴呆。

Objective:To study the effects of Danggui Buxue Decoction(DBD)on learning,memory,antioxidation and cholinergic neurotransmitters of vascular dementia rats.Methods:Wistar rats were randomly divided into the sham group,model group,piracetam(0.324 g/kg)group,and low-(36 g/kg)and high-dose(54 g/kg)DBD groups and orally administrated with the corresponding drugs or normal saline,once a day,for 30 days.The Morris water maze was used to conduct place and spatial probe tests.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-PX),malondialdehyde(MDA),acetylcholine(Ach),and acetylcholinesterase(AchE)activities were measured in cerebral cortex and hippocampus of rats from each group.HE staining was carried out to observe the structure changes in hippocampus.Results:As revealed by the place and spatial probe tests in Morris water maze,the escape latency of the model group was significantly prolonged on the 5 th day as compared with that in the sham group(P<0.01),while the residence time on the escape platform,the movement time in the effective area,and the frequency of entry into the escape platform were significantly decreased(P<0.01).The comparison with the model group showed that the escape latency in each drug administration group was significantly shortened on the 5 th day(P<0.01),whereas the residence time on the escape platform,the movement time in the effective area,and the frequency of entry into the escape platform were significantly increased(P<0.01).Compared with the sham group,the model group exhibited significantly elevated MDA(P<0.01)but lowered GSH-PX and SOD activities in the cerebral cortex(P<0.01 or P<0.05)and significantly decreased Ach content(P<0.01)but weakened AchE activity in the hippocampus(P<0.01).Compared with the model group,each drug administration group displayed significantly reduced MDA content(P<0.01),enhanced GSH-PX and SOD activities(P<0.01 or P<0.05),and increased Ach(P<0.01).The activities of AchE in all drug administration groups except for the 0.324 g/kg piracetam group were significantly reduced(P<0.01).The pathological changes in rat hippocampus were improved in all administration groups.Conclusion:DBD ameliorates the learning and memory ability of rats with vascular dementia by improving the antioxidant enzyme activity,promoting the release of cholinergic neurotransmitters,and inhibiting AchE activity.