目的探讨丹参多酚酸对抑郁大鼠认知功能障碍的影响。方法92只体质量110～150g清洁级雄性sD大鼠，按随机数字法分为5组，即非应激＋生理盐水组（对照组），n=19，应激＋生理盐水组（生理盐水组，n=19），应激＋氟西汀组（氟西汀组，n=18...目的探讨丹参多酚酸对抑郁大鼠认知功能障碍的影响。方法92只体质量110～150g清洁级雄性sD大鼠，按随机数字法分为5组，即非应激＋生理盐水组（对照组），n=19，应激＋生理盐水组（生理盐水组，n=19），应激＋氟西汀组（氟西汀组，n=18），应激＋丹酚酸组（丹酚酸组，n=20），应激＋氟西汀＋丹酚酸组（联合组，n=16）。采用慢性温和应激（Chronic mild stress，CMS）建立抑郁大鼠模型，造模成功后，应激各组继续给予应激，且每天腹腔分别注射氟西汀20mg·kg^-1、丹参多酚酸40mg·kg^-1、氟西汀20mg·kg^-1＋丹参多酚酸40mg·kg^-1及等体积生理盐水，体积体质量比10ml·kg^-1。应激3周后、给药3周后测体质量（g）、计算体质量增加值（g）、蔗糖偏好率（％），采用Morris水迷宫实验（Morris water maze，MWM）来评定大鼠认知功能。结果应激3周后：5组大鼠的体质量差异有统计学意义（F=11．828，P〈0．01），对照组的体质量高于应激各组（均P〈0．01）；对照组蔗糖偏好率高于其他组（均P〈0．05）；水迷宫前5d测试显示5组之间差异有统计学意义（F=5．732，P〈0．01），测量时间之间差异有统计学意义（F=136．000，P〈0．01），对照组逃避潜伏期低于其他组（均P〈0．05）。对照组第6天穿越平台象限时间高于其他应激4组（均P〈0．01）。给药3周后：生理盐水组的体质量增加值低于氟西汀、丹酚酸、联合组（均P〈0．01）；氟西汀、丹酚酸、联合组的蔗糖偏好率高于生理盐水组（均P〈0．01）；前5d，5组大鼠MWM逃避潜伏期差异有统计学意义（F=16．243，P〈0．01），测量时间之间差异有统计学意义（F=9．359，P〈0．01）。第6天穿越平台象限时间差异有统计学意义（F=14．499，P〈0．01）。生理盐水组第6天穿越平台象限时间[（9．39±2．22）s]低于对照组[（16．93±4．49）s]，�展开更多
ETS-1 is a transcription factor that is a member of the E26 transformation-specific(ETS) family. Galanin receptor 2(Gal R2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant...ETS-1 is a transcription factor that is a member of the E26 transformation-specific(ETS) family. Galanin receptor 2(Gal R2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant-like effect after activation in rodents. Our previous study has shown that overexpression of ETS-1 increases the expression of Gal R2 in PC12 phaeochromocytoma cells. However, whether ETS-1 has an antidepressant-like effect is still unclear. In this study, we found that chronic mild stress(CMS) decreased the expression of both ETS-1 and Gal R2 in the ventral hippocampus of rats. Meanwhile,we demonstrated that overexpression of ETS-1 increased the expression of Gal R2 in primary hippocampal neurons.Importantly, we showed that overexpression of ETS-1 in the ventral hippocampus counteracted the depression-like behaviors of CMS rats. Furthermore, we found that overexpression of ETS-1 increased the level of downstream phosphorylated extracellular signal-regulated protein kinases 1 and 2(p-ERK1/2) of Gal R2 in the ventral hippocampus of CMS rats. Taken together, our findings suggest that ETS-1 has an antidepressant-like effect in rats,which might be mediated by increasing the level of Gal R2 and its downstream p-ERK1/2 in the ventral hippocampus.展开更多
文摘目的探讨丹参多酚酸对抑郁大鼠认知功能障碍的影响。方法92只体质量110～150g清洁级雄性sD大鼠，按随机数字法分为5组，即非应激＋生理盐水组（对照组），n=19，应激＋生理盐水组（生理盐水组，n=19），应激＋氟西汀组（氟西汀组，n=18），应激＋丹酚酸组（丹酚酸组，n=20），应激＋氟西汀＋丹酚酸组（联合组，n=16）。采用慢性温和应激（Chronic mild stress，CMS）建立抑郁大鼠模型，造模成功后，应激各组继续给予应激，且每天腹腔分别注射氟西汀20mg·kg^-1、丹参多酚酸40mg·kg^-1、氟西汀20mg·kg^-1＋丹参多酚酸40mg·kg^-1及等体积生理盐水，体积体质量比10ml·kg^-1。应激3周后、给药3周后测体质量（g）、计算体质量增加值（g）、蔗糖偏好率（％），采用Morris水迷宫实验（Morris water maze，MWM）来评定大鼠认知功能。结果应激3周后：5组大鼠的体质量差异有统计学意义（F=11．828，P〈0．01），对照组的体质量高于应激各组（均P〈0．01）；对照组蔗糖偏好率高于其他组（均P〈0．05）；水迷宫前5d测试显示5组之间差异有统计学意义（F=5．732，P〈0．01），测量时间之间差异有统计学意义（F=136．000，P〈0．01），对照组逃避潜伏期低于其他组（均P〈0．05）。对照组第6天穿越平台象限时间高于其他应激4组（均P〈0．01）。给药3周后：生理盐水组的体质量增加值低于氟西汀、丹酚酸、联合组（均P〈0．01）；氟西汀、丹酚酸、联合组的蔗糖偏好率高于生理盐水组（均P〈0．01）；前5d，5组大鼠MWM逃避潜伏期差异有统计学意义（F=16．243，P〈0．01），测量时间之间差异有统计学意义（F=9．359，P〈0．01）。第6天穿越平台象限时间差异有统计学意义（F=14．499，P〈0．01）。生理盐水组第6天穿越平台象限时间[（9．39±2．22）s]低于对照组[（16．93±4．49）s]，�
基金supported by grants from the National Natural Science Foundation of China (31271154, 31171032, and 81671345)the Beijing Natural Science Foundation (7162016)+1 种基金the Special Project on Natural Chronic Non-infectious Diseases (2016YFC1307202)the Beijing Municipal Science and Technology Commission (Z181100001518001)
文摘ETS-1 is a transcription factor that is a member of the E26 transformation-specific(ETS) family. Galanin receptor 2(Gal R2), a subtype of receptors of the neuropeptide galanin, has been shown to have an antidepressant-like effect after activation in rodents. Our previous study has shown that overexpression of ETS-1 increases the expression of Gal R2 in PC12 phaeochromocytoma cells. However, whether ETS-1 has an antidepressant-like effect is still unclear. In this study, we found that chronic mild stress(CMS) decreased the expression of both ETS-1 and Gal R2 in the ventral hippocampus of rats. Meanwhile,we demonstrated that overexpression of ETS-1 increased the expression of Gal R2 in primary hippocampal neurons.Importantly, we showed that overexpression of ETS-1 in the ventral hippocampus counteracted the depression-like behaviors of CMS rats. Furthermore, we found that overexpression of ETS-1 increased the level of downstream phosphorylated extracellular signal-regulated protein kinases 1 and 2(p-ERK1/2) of Gal R2 in the ventral hippocampus of CMS rats. Taken together, our findings suggest that ETS-1 has an antidepressant-like effect in rats,which might be mediated by increasing the level of Gal R2 and its downstream p-ERK1/2 in the ventral hippocampus.
