摘要
目的探究麦冬皂苷D对阿尔茨海默病(AD)模型大鼠认知功能障碍的作用及其机制。方法将72只大鼠随机分为假手术组、模型组、麦冬皂苷D 10 mg/kg组、麦冬皂苷D 20 mg/kg组、麦冬皂苷D 40 mg/kg组和盐酸多奈哌齐组,每组12只。除假手术组外,其余各组均建立AD大鼠模型,药物干预4周。水迷宫试验检测大鼠认知能力;HE染色检测海马组织病理变化;尼氏染色检测海马组织尼氏体变化,评估神经元情况;检测海马组织氧化应激指标丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平和乙酰胆碱转移酶(ChAT)、乙酰胆碱(Ach)、乙酰胆碱酯酶(AChE)水平;Western blot检测脑源性神经营养因子(BDNF)、酪氨酸激酶受体B(TrkB)蛋白表达水平。结果与假手术组比较,模型组大鼠逃跑潜伏期延长(P<0.05),穿越目标象限次数减少(P<0.05),在目标象限停留时间缩短(P<0.05);与模型组比较,麦冬皂苷D 20 mg/kg组、40 mg/kg组和盐酸多奈哌齐组大鼠逃跑潜伏期均缩短(P<0.05),穿越目标象限次数增加(P<0.05),在目标象限停留时间延长(P<0.05)。模型组较假手术组出现明显神经元排列紊乱、海马组织空洞增多,尼氏体数量减少,麦冬皂苷D 20 mg/kg组、40 mg/kg组和盐酸多奈哌齐组较模型组海马组织病理情况出现不同程度的改善,尼氏体数量增多。与假手术组比较,模型组大鼠海马组织MDA、AChE水平升高(P<0.05),SOD、GSH-Px、ChAT、Ach水平降低(P<0.05),BDNF、TrkB蛋白表达水平均下调(P<0.05);与模型组比较,麦冬皂苷D 20 mg/kg组、40 mg/kg组和盐酸多奈哌齐组大鼠海马组织MDA、AChE水平降低(P<0.05),SOD、GSH-Px、ChAT、Ach水平升高(P<0.05),BDNF、TrkB蛋白表达水平均上调(P<0.05)。结论麦冬皂苷D可改善AD大鼠认知功能障碍,减轻氧化应激,调节神经递质平衡,其机制可能与调控BDNF/TrkB信号通路相关。
Objective To explore the effect and mechanism of ophiopogonin D on cognitive dysfunction of model rats with Alzheimer’s disease(AD).Methods A total of 72 rats were randomly divided into the sham operation group,the model group,the ophiopogonin D 10 mg/kg group,the ophiopogonin D 20 mg/kg group,the ophiopogonin D 40 mg/kg group and the donepezil hydrochloride group,with 12 rats in each group.Except for the sham operation group,AD rat models were established in other groups,and the drug intervention lasted for 4 weeks.The cognitive ability of rats was detected by water maze test,and the pathological changes of hippocampal tissues were detected by HE staining.Nissl staining was used to detect the Nissl body changes of hippocampal tissues,and the condition of neurons was evaluated.The levels of oxidative stress indicators of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),choline acetyltransferase(ChAT),acetylcholine(Ach)and acetyl cholinesterase(AChE)of hippocampal tissues were detected.Western blot was used to detect the protein expression levels of brain-derived neurotrophic factor(BDNF)and tyrosine kinase receptor B(TrkB).Results Compared with the sham operation group,the escape latency of rats in the model group was lengthened(P<0.05),the frequency of crossing the target quadrant was reduced(P<0.05),and the stay time in the target quadrant was shortened(P<0.05).Compared with the model group,the escape latency of rats in ophiopogonin D 20 mg/kg and 40 mg/kg groups and the donepezil hydrochloride group were shortened(P<0.05),the frequency of crossing the target quadrant was increased(P<0.05),and the stay time in the target quadrant was prolonged(P<0.05).The neurons in the model group were significantly disordered,the hippocampal cavity was increased and the number of Nissl bodies was decreased compared to the sham operation group,and the hippocampal histopathology showed different degrees of improvement and the number of Nissl bodies was increased in ophiopogonin D 20 mg/kg and 40 mg/kg groups and the donepezil hydrochloride group compared to the model group.Compared with the sham operation group,the levels of MDA and AChE in hippocampal tissues of rats in the model group were increased(P<0.05),while the levels of SOD,GSH-Px,ChAT and Ach were reduced(P<0.05),and the protein expression levels of BDNF and TrkB were down-regulated(P<0.05).Compared with the model group,the levels of MDA and AChE in hippocampal tissues of rats in ophiopogonin D 20 mg/kg and 40 mg/kg groups and the donepezil hydrochloride group were reduced(P<0.05),while the levels of SOD,GSH-Px,ChAT and Ach were increased(P<0.05),and the protein expression levels of BDNF and TrkB were up-regulated(P<0.05).Conclusion Ophiopogonin D can improve the cognitive dysfunction of rats with AD,reduce oxidative stress,regulate the balance of neurotransmitters,which may be related to regulation of BDNF/TrkB signaling pathways.
作者
李倩
张烨君
李燃
岳宇坤
娄展
LI Qian;ZHANG Ye-jun;LI Ran;YUE Yu-kun;LOU Zhan(Third Department of Neurology,First Affiliated Hospital of Hebei North University,Zhangjiakou Hebei 075000,China)
出处
《局解手术学杂志》
2022年第12期1046-1051,共6页
Journal of Regional Anatomy and Operative Surgery
基金
张家口市重点研发计划项目(2121159D)。
