龟鹿二仙胶对创伤后应激障碍模型大鼠行为学及海马GR、5-HT受体表达的影响
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摘要
目的:观察龟鹿二仙胶对创伤后应激障碍(posttraumatic stress disorder,PTSD)模型大鼠行为学,海马糖皮质激素受体(glucocorticoid receptors,GR)及5-羟色胺(5-hydroxytryptamine,5-HT)受体1A亚型(5-HT1A)、2A亚型(5-HT2A)表达的影响。方法:采用单一延长刺激方法制作大鼠PTSD模型,通过旷场实验、拒俘反应实验以及Morris水迷宫实验观察大鼠的情感行为和学习记忆能力的改变。采用RT-PCR法检测海马GR、5-HT1A和5-HT2A受体表达。结果:PTSD大鼠表现出多种情感行为障碍,学习能力显著降低(P<0.01)。海马GR表达增强(P<0.01),5-HT1A受体表达下降(P<0.05),5-HT2A受体表达则升高(P<0.05)。龟鹿二仙胶(2.025 g·kg~(-1))和淫羊藿总黄酮(0.06 g·kg~(-1))能显著改善PTSD大鼠的情感行为障碍,提高学习记忆能力(P<0.05或P<0.01)。龟鹿二仙胶(2.025 g·kg~(-1))和淫羊藿总黄酮(0.06 g·kg~(-1))可以明显降低PTSD大鼠海马GR的表达水平,升高5-HT1A受体表达水平和降低5-HT2A受体表达水平(P<0.05或P<0.01)。结论:龟鹿二仙胶对PTSD具有良好的干预治疗作用,其作用机理与改善情感行为和认知功能以及调节海马GR、5-HT1A和5-HT2A受体表达有关。
Objective: To observe the effects of Guilu Erxian Glue on behavior,glucocorticoid receptors( GR) and 5-hydroxytryptamine( 5-HT) receptor subtypes 1 A( 5-HT1 A) and 2 A( 5-HT2 A) expression in posttraumatic stress disorder( PTSD) rats. Methods: Rat PTSD model was established by a single prolonged stimulation method. The emotional behavior and learning and memory ability of rats were observed by open field experiment,anti-capture reaction experiment and Morris water maze test. RT-PCR was used to detect the expression of GR,5-HT1 A and 5-HT2 A receptors in hippocampus. Results: PTSD rats showed a variety of emotional behavioral disorders,and their learning ability was significantly lower( P < 0. 01). The expression of GR in hippocampus was enhanced( P < 0. 01),the expression of 5-HT1 A receptor was decreased( P < 0. 05),and the expression of 5-HT2 A receptor was increased( P < 0. 05). Guilu Erxian Glue( 2. 025 g · kg-1) and Epimedium total flavonoids( 0. 06 g·kg-1) can significantly improve the emotional behavior disorder of PTSD rats and improve learning and memory ability( P <0. 05 or P < 0. 01).). Guilu Erxian Glue( 2. 025 g·kg-1) and Epimedium total flavonoids( 0. 06 g·kg-1) can significantly reduce the expression of GR in hippocampus of PTSD rats,increase the expression level of 5-HT 1 Areceptor and The expression level of 5-HT2 A receptor was decreased( P < 0. 05 or P < 0. 01). Conclusion: Guilu Erxian Glue has a good intervention effect on PTSD,and its mechanism is related to improving emotional behavior and cognitive function and regulating hippocampal GR,5-HT1 A and 5-HT2 A receptor expression.
Objective: To observe the effects of Guilu Erxian Glue on behavior,glucocorticoid receptors( GR) and 5-hydroxytryptamine( 5-HT) receptor subtypes 1 A( 5-HT1 A) and 2 A( 5-HT2 A) expression in posttraumatic stress disorder( PTSD) rats. Methods: Rat PTSD model was established by a single prolonged stimulation method. The emotional behavior and learning and memory ability of rats were observed by open field experiment,anti-capture reaction experiment and Morris water maze test. RT-PCR was used to detect the expression of GR,5-HT1 A and 5-HT2 A receptors in hippocampus. Results: PTSD rats showed a variety of emotional behavioral disorders,and their learning ability was significantly lower( P < 0. 01). The expression of GR in hippocampus was enhanced( P < 0. 01),the expression of 5-HT1 A receptor was decreased( P < 0. 05),and the expression of 5-HT2 A receptor was increased( P < 0. 05). Guilu Erxian Glue( 2. 025 g · kg-1) and Epimedium total flavonoids( 0. 06 g·kg-1) can significantly improve the emotional behavior disorder of PTSD rats and improve learning and memory ability( P <0. 05 or P < 0. 01).). Guilu Erxian Glue( 2. 025 g·kg-1) and Epimedium total flavonoids( 0. 06 g·kg-1) can significantly reduce the expression of GR in hippocampus of PTSD rats,increase the expression level of 5-HT 1 Areceptor and The expression level of 5-HT2 A receptor was decreased( P < 0. 05 or P < 0. 01). Conclusion: Guilu Erxian Glue has a good intervention effect on PTSD,and its mechanism is related to improving emotional behavior and cognitive function and regulating hippocampal GR,5-HT1 A and 5-HT2 A receptor expression.
引文
[1]郭宏伟.中医药拮抗创伤后应激障碍的研究现状[J].中国实验方剂学杂志,2018,24(2):213-219.
[2]顾雯,刘真,苑广哲,等.虚拟现实暴露疗法在创伤后应激障碍治疗中的应用[J].中国临床心理学杂志,2018,26(2):1246-1251.
[3]吴丽丽,严灿,刘书考.肾虚对恐惧记忆形成的影响及补肾方药调节作用的初步研究[J].安徽中医学院学报,2012,31(3):48-52.
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[5]YOUNG N A,WINTINK A J,KALYNCHUK L E.Environmental enrichment facilitates amygdala kindling but reduces kindling-induced fear in male rats[J].Behav Neurosci,2004,118(5):1128-1133.
[6]DASH P K,ZHAO J,ORSI S A,et al.Sulforaphane improves cognitive function administered following traumatic brain injury[J].Neurosci Lett,2009,460(2):103-107.
[7]LI G H,KATAKURA M,MARUYAMA M,et al.Changes of noradrenaline-induced contractility and gene expression in aorta of rats acclimated to heat in two different models[J].Eur J Appl Physiol,2008,104(1):29-40.
[8]WANG W,LIU Y,ZHENG H,et al.A modified single-prolonged stress model for post-traumatic stress disorder[J].Neurosci Lett,2008,441(2):237-241.
[9]向阳,王庆松,郑宇.反复惊厥阈下痫样放电致大鼠持续性情绪唤醒障碍[J].中国神经精神疾病杂志,2011,37(11):694-698.
[10]张景华,李慢,石玉秀,等.创伤后应激障碍大鼠前额叶内侧皮质糖皮质激素受体表达增高[J].解剖学报,2011,42(2):151-154.
[11]QUERVAIN D J,MARGRAF J.Glucocorticoids for the treatment of posttraumatic stress disorder and phobias:novel therapeutic approach[J].Eur J Pharmacol,2008,583(2/3):365-371.
[12]FANSELOW M S.Contextual fear,gestalt memories,and the hippocampus[J].Behavioural Brain Research,2000,110(1/2):73-81.
[13]ROGALSKA J.Mineralocorticoid and glucocorticoid receptors in hippocampus:their impact on neurons survival and behavioral impairment after neonatal brain injury[J].Vitam Horm,2010,82:391-419.
[14]PARIANTE C M,MILLER A H.Glucocorticoid receptors in major depression:relevance to pathophysiology and treatment[J].Biol Psychiatry,2001,49(5):391-404.
[15]侯良芹,刘嵩,熊克仁.电针对创伤后应激障碍大鼠行为学和海马糖皮质激素受体表达的影响[J].针刺研究,2013,38(2):140-145.
[16]INOUE T,KITAICHI Y,KOYAMA T.SSRIs and conditioned fear[J].Prog Neuro Psychopharmacol Biol Psychiatry,2011,35(8):1810-1819.
[17]MURROUGH JW,HUANG Y,HU J,et al.Reduced Amygdala Serotonin Transporter Binding in Posttraumatic Stress Disorder[J].Biol Psychiatry,2011,70(11):1033-1038.
[18]BLIER P,WARD N M.Is there a role for 5-HT1A agonists in the treatment of depression[J]?Biol Psychiatry,2003,53(3):193-203.
[19]LIU H,WANG H T,HAN F,et al.Activity of 5-HT1A receptor is involved in neuronal apoptosis of the amygdala in a rat model of post-traumatic stress disorder[J].Mol Med Rep,2011,4(2):291-295.
[20]张黎明,陈红霞,张有志,等.5-羟色胺与创伤后应激障碍的研究进展[J].中国药理学通报,2010,26(10):1261-1263.
[21]Doinon S E,Andersen M S.Nefazodone for ptsd[J].J Am Acad Child Adolesc Psychiatry,2000,39(8):942-943.
[22]张辉,张先庚,高静,等.创伤后压力心理障碍中医治疗研究进展[J].吉林中医药,2015,35(10):1077-1079.
[23]彭晓明,丁晓华,陈开兵,等.金匮肾气丸联合帕罗西汀对创伤后应激障碍的疗效观察[J].世界睡眠医学杂志,2018,5(5):534-553
[24]冯晓芬,王玉萍.滋补肾精方对雌性肾虚小鼠内分泌调节功能影响的实验研究[J].中医研究,2010,23(3):14-17.
[25]张鹏,谢磊,罗瑞,等.温补肾阳方对创伤后应激障碍大鼠行为学及血浆17-OHCS、cAMP 影响的研究[J].四川中医,2011,29(9):19-21.
[2]顾雯,刘真,苑广哲,等.虚拟现实暴露疗法在创伤后应激障碍治疗中的应用[J].中国临床心理学杂志,2018,26(2):1246-1251.
[3]吴丽丽,严灿,刘书考.肾虚对恐惧记忆形成的影响及补肾方药调节作用的初步研究[J].安徽中医学院学报,2012,31(3):48-52.
[4]PETERS B J,JAMIESON J P.The consequences of suppressing affective displays in romantic relationships:A challenge and threat perspective[J].Emotion,16(7):1050-1066.
[5]YOUNG N A,WINTINK A J,KALYNCHUK L E.Environmental enrichment facilitates amygdala kindling but reduces kindling-induced fear in male rats[J].Behav Neurosci,2004,118(5):1128-1133.
[6]DASH P K,ZHAO J,ORSI S A,et al.Sulforaphane improves cognitive function administered following traumatic brain injury[J].Neurosci Lett,2009,460(2):103-107.
[7]LI G H,KATAKURA M,MARUYAMA M,et al.Changes of noradrenaline-induced contractility and gene expression in aorta of rats acclimated to heat in two different models[J].Eur J Appl Physiol,2008,104(1):29-40.
[8]WANG W,LIU Y,ZHENG H,et al.A modified single-prolonged stress model for post-traumatic stress disorder[J].Neurosci Lett,2008,441(2):237-241.
[9]向阳,王庆松,郑宇.反复惊厥阈下痫样放电致大鼠持续性情绪唤醒障碍[J].中国神经精神疾病杂志,2011,37(11):694-698.
[10]张景华,李慢,石玉秀,等.创伤后应激障碍大鼠前额叶内侧皮质糖皮质激素受体表达增高[J].解剖学报,2011,42(2):151-154.
[11]QUERVAIN D J,MARGRAF J.Glucocorticoids for the treatment of posttraumatic stress disorder and phobias:novel therapeutic approach[J].Eur J Pharmacol,2008,583(2/3):365-371.
[12]FANSELOW M S.Contextual fear,gestalt memories,and the hippocampus[J].Behavioural Brain Research,2000,110(1/2):73-81.
[13]ROGALSKA J.Mineralocorticoid and glucocorticoid receptors in hippocampus:their impact on neurons survival and behavioral impairment after neonatal brain injury[J].Vitam Horm,2010,82:391-419.
[14]PARIANTE C M,MILLER A H.Glucocorticoid receptors in major depression:relevance to pathophysiology and treatment[J].Biol Psychiatry,2001,49(5):391-404.
[15]侯良芹,刘嵩,熊克仁.电针对创伤后应激障碍大鼠行为学和海马糖皮质激素受体表达的影响[J].针刺研究,2013,38(2):140-145.
[16]INOUE T,KITAICHI Y,KOYAMA T.SSRIs and conditioned fear[J].Prog Neuro Psychopharmacol Biol Psychiatry,2011,35(8):1810-1819.
[17]MURROUGH JW,HUANG Y,HU J,et al.Reduced Amygdala Serotonin Transporter Binding in Posttraumatic Stress Disorder[J].Biol Psychiatry,2011,70(11):1033-1038.
[18]BLIER P,WARD N M.Is there a role for 5-HT1A agonists in the treatment of depression[J]?Biol Psychiatry,2003,53(3):193-203.
[19]LIU H,WANG H T,HAN F,et al.Activity of 5-HT1A receptor is involved in neuronal apoptosis of the amygdala in a rat model of post-traumatic stress disorder[J].Mol Med Rep,2011,4(2):291-295.
[20]张黎明,陈红霞,张有志,等.5-羟色胺与创伤后应激障碍的研究进展[J].中国药理学通报,2010,26(10):1261-1263.
[21]Doinon S E,Andersen M S.Nefazodone for ptsd[J].J Am Acad Child Adolesc Psychiatry,2000,39(8):942-943.
[22]张辉,张先庚,高静,等.创伤后压力心理障碍中医治疗研究进展[J].吉林中医药,2015,35(10):1077-1079.
[23]彭晓明,丁晓华,陈开兵,等.金匮肾气丸联合帕罗西汀对创伤后应激障碍的疗效观察[J].世界睡眠医学杂志,2018,5(5):534-553
[24]冯晓芬,王玉萍.滋补肾精方对雌性肾虚小鼠内分泌调节功能影响的实验研究[J].中医研究,2010,23(3):14-17.
[25]张鹏,谢磊,罗瑞,等.温补肾阳方对创伤后应激障碍大鼠行为学及血浆17-OHCS、cAMP 影响的研究[J].四川中医,2011,29(9):19-21.