摘要
目的以斑马鱼为模型,研究海洋深层水(deep-sea water,DSW)对氯化铝(AlCl3)诱导所致阿尔茨海默病(Alzheimer’s disease,AD)的干预作用,初步探讨DSW防治AD的可能机制。方法采用AlCl3诱导斑马鱼成鱼建立AD模型,建模的同时给予不同硬度的DSW,通过Viewpoint斑马鱼行为分析系统和T迷宫装置观察DSW对AD斑马鱼自主活动能力和学习认知能力的影响;最后通过Western Blot检测Tau蛋白的表达及磷酸化程度。结果与空白对照组相比,AlCl3暴露的模型组斑马鱼的游行距离和最大速度显著降低,进入偏爱营养丰富区(enriched chamber,EC)的潜伏时间显著增加,而在EC区的停留时间显著降低,说明其自主活动能力、学习和空间认知能力明显受到影响,AlCl3诱导成功建立AD模型;而DSW可以提高AD斑马鱼的游行距离和速度,降低其进入EC区的潜伏时间,延长其在EC区的停留时间,并呈剂量依赖性,说明DSW可以改善AlCl3诱导所致AD斑马鱼的自主活动能力和学习认知能力。Western blot表明,DSW可以显著抑制Tau蛋白在丝氨酸(serine,Ser)396及苏氨酸(Threonine,Thr)231这2个位点的过度磷酸化。结论 DSW可以有效改善AD,其作用机制可能与抑制Tau蛋白的过度磷酸化有关。
Objective To investigate the protective effect and possible mechanism of deep sea water(DSW)against Alzheimer’s disease(AD)in zebrafish model.Methods The adult zebrafish were exposed to AlCl3 of 50μg/L to induce an AD model,at the same time zebrafish were treated with DSW of different hardness.The locomotor activity,learning and memory behavior of zebrafish under different treatment were studied with the T-maze experiment,the expression and phosphorylation levels of Tau protein were detected by Western blot.Results The results showed that,compared with the control group,exposure of zebrafish to 50μg/L AlCl3 for 96 hsignificantly decreased travel distance and speed of fish in model group.What’s more,in the T-maze behavior test,the latency time of model group at entering specified arms of T-maze increased significantly,while the residence time in EC area decreased,compared to the control.However,the latency time of all the DSW exposure groups decreased significantly with the increase of exposure concentration and the extension of exposure time.Western Blot indicated that,in AlCl3 exposed group the phosphorylation levels of Tau protein in Ser 396 and Thr 231 were significantly increased.After the interference with different hardness of DSW,levels of phosphorylation of Tau protein were significantly lower in a dose-dependent manner.Conclusion DSW could alleviate AD in zebrafish model,which might be associated with arresting Tau hyperphosphorylation.
作者
何珊
彭维兵
周洪雷
付先军
HE Shan;PENG Wei-bing;ZHOU Hong-lei;FU Xian-jun(School of Pharmacology,Shandong University of Traditional Chinese Medicine,Jinan 250355,China;Biology Institute,Qilu University of Technology (Shandong Academy of Sciences),Jinan 250014,China;Institute of TCM Literature,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)
出处
《中国海洋药物》
CAS
CSCD
2019年第3期45-51,共7页
Chinese Journal of Marine Drugs
基金
山东省自然科学基金项目(ZR2019BH016)
山东中医药大学科研创新团队建设项目——中医药经典理论传承与创新应用研究团队(220304)资助
