欧前胡素抗抑郁作用及机制研究
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摘要
目的探讨欧前胡素(IMP)的抗抑郁作用及其机制。方法采用产前束缚应激对孕后期♀鼠建立抑郁模型,将SD♂子代大鼠随机分为5组,每组8只。分别是正常组(CON)、模型组(PS)、阳性组(氟西汀5 mg·kg~(-1)·d~(-1))、IMP低、高剂量组(15、30 mg·kg~(-1)·d~(-1))。均采用灌胃给药,每天1次,连续给药4周。进行糖水偏好、强迫游泳、旷场实验行为学测试,ELISA法、实时定量PCR检测海马及前额叶皮层中5-HT的浓度、5-HTT和5-HT_(1A)R的mRNA表达量。结果 IMP给药4周后,与PS组相比,IMP组糖水偏好度明显上升,不动时间减少,穿越总格子数、穿越中间格子数、直立和理毛次数明显增加(P<0.05,P<0.01),5-HT的浓度及5-HT_(1A)R的mRNA表达明显升高(P<0.05,P<0.01),5-HTT mRNA的表达明显降低(P<0.05,P<0.01)。结论 IMP可明显改善PS♂子代抑郁样行为,具有抗抑郁作用,其机制可能与升高5-HT浓度及5-HT1A R mRNA的表达,降低5-HTT mRNA的表达有关。
Aim To investigate the antidepressant effect of imperatorin(IMP) and explore its mechanism. Methods The model of depression was established by prenatal stress(PS) on late pregnant mother, then male offspring rats were randomly divided into five groups: control, PS model, fluoxetine group(5 mg·kg~(-1)), IMP(15, 30 mg·kg~(-1)). Sucrose preference test, forced swimming test, and open field test were used to evaluate the behavioral changes. 5-hydroxytryptamine(5-HT) concentration, serotonin transporters(5-HTT) and 5-HT_(1 A) receptor(5-HT_(1 A)R) mRNA expression in the hippocampus and frontal cortex were measured using an enzyme-linked immunosorbent assay and real-time PCR. Results Compared with PS group, the percentage of sucrose preference and the number of total crossings, center crossings, rearing, grooming and 5-HT concentration significantly increased in IMP group(P<0.05,P<0.01). The immobility time was significantly reduced in IMP group compared with PS group(P<0.01). The 5-HT concentration and 5-HT_(1 A)R mRNA expressions of PS offspring rats significantly increased by the administration of IMP(P<0.05,P<0.01). And, the increased 5-HTT mRNA markedly decreased in IMP group compared with PS group(P<0.05,P<0.01). Conclusions IMP can obviously improve rat behavior and show anti-depressant effect, which may relate to the 5-HT concentration, 5-HTT and 5-HT_(1 A)R mRNA expression in hippocampus and prefrontal cortex.
Aim To investigate the antidepressant effect of imperatorin(IMP) and explore its mechanism. Methods The model of depression was established by prenatal stress(PS) on late pregnant mother, then male offspring rats were randomly divided into five groups: control, PS model, fluoxetine group(5 mg·kg~(-1)), IMP(15, 30 mg·kg~(-1)). Sucrose preference test, forced swimming test, and open field test were used to evaluate the behavioral changes. 5-hydroxytryptamine(5-HT) concentration, serotonin transporters(5-HTT) and 5-HT_(1 A) receptor(5-HT_(1 A)R) mRNA expression in the hippocampus and frontal cortex were measured using an enzyme-linked immunosorbent assay and real-time PCR. Results Compared with PS group, the percentage of sucrose preference and the number of total crossings, center crossings, rearing, grooming and 5-HT concentration significantly increased in IMP group(P<0.05,P<0.01). The immobility time was significantly reduced in IMP group compared with PS group(P<0.01). The 5-HT concentration and 5-HT_(1 A)R mRNA expressions of PS offspring rats significantly increased by the administration of IMP(P<0.05,P<0.01). And, the increased 5-HTT mRNA markedly decreased in IMP group compared with PS group(P<0.05,P<0.01). Conclusions IMP can obviously improve rat behavior and show anti-depressant effect, which may relate to the 5-HT concentration, 5-HTT and 5-HT_(1 A)R mRNA expression in hippocampus and prefrontal cortex.
引文
[1] 张兵,李扬.针对谷氨酸能系统的抗抑郁药物的研究进展[J].中国药理学通报,2014,30(9):1197-2000.
[1] Zhang B, Li Y. Research progress of the antidepressants targeting the glutamate receptors[J]. Chin Pharmacol Bull,2014,30(9):1197-2000.
[2] Luszczki J J, Wojda E, Andres-Mach M, et al. Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: a comparative study[J]. Epilepsy Res,2009, 85(2-3): 293-9.
[3] 郑莉明,史亚飞,吴皓萌,等.中枢5-HT能系统在早发性抑郁中的作用研究[J].中国药理学通报,2015,31(1):19-23.
[3] Zheng L M, Shi Y F, Wu H M, et al. Research on effect of central 5-HTergic system in early-onset depression[J]. Chin Pharmacol Bull, 2015,31(1):19-23.
[4] 陈红霞,张黎明,薛瑞,等.以5-HT1A受体为靶标的抗抑郁药物研究进展[J]. 军事医学,2013,37(8):624-30.
[4] Chen H X, Zhang L M, Xue R, et al. Progress of antidepressant drugs based on 5-HT1A receptor as a new target[J]. Milit Med Sci,2013,37(8):624-30.
[5] Sharp T, Cowen P J. 5-HT and depression: is the glass half-full[J]. Curr Opin Pharmacol,2011,11(1):45-51.
[6] Kiryanova V, Meunier S J, Dyck R H. Behavioural outcomes of adult female offspring following maternal stress and perinatal fluoxetine exposure[J]. Behav Brain Res,2017,331(7):84-91.
[7] Budzynska B, Boguszewska-Czubara A, Kruk-Slomka M, et al. Effects of imperatorin on scopolamine-induced cognitive impairment and oxidative stress in mice[J]. Psychopharmacology,2015, 232(5): 931-42.
[8] Shi M M, Piao J H, Xu X L, et al. Chinese medicines with sedative-hypnotic effects and their active components[J]. Sleep Med Rev,2016, 29(3):108-18.
[9] Wang S S, Mu R H, Li C F, et al. MicroRNA-124 targets glucocorticoid receptor and is involved in depression-like behaviors[J]. Prog Neuropsychopharmacology Biol Psychiatry,2017,79(ptB):417-25.
[10] Fatima M, Srivastav S, Mondal A C. Prenatal stress and depression associated neuronal development in neonates[J]. Int J Dev Neurosci,2017,60:1-7.
[11] Cao Y J, He X, Wang N, et al. Effects of imperatorin, the active component from Radix Angelicae(Baizhi), on the blood pressure and oxidative stress in 2K,1C hypertensive rats[J]. Phytomedicine, 2013, 20(12): 1048-54.
[12] Han X, Wu H, Yin P, et al. Electroacupuncture restores hippocampal synaptic plasticity via modulation of 5-HT receptors in a rat model of depression[J]. Brain Res Bull, 2018,139:256-62.
[13] ?uszczki J J, Andres-Mach M, Gleńsk M, et al. Anticonvulsant effects of four linear furanocoumarins, bergapten, imperatorin, oxypeucedanin, and xanthotoxin, in the mouse maximal electroshock-induced seizure model: a comparative study[J]. Pharmacol Rep, 2010,62(6): 1231-6.
[14] Wang S J, Lin T Y, Lu C W, et al. Osthole and imperatorin, the active constituents of Cnidium monnieri(L.) Cusson, facilitate glutamate release from rat hippocampal nerve terminals[J]. Neurochem Int, 2008, 53(6-8): 416-23.
[1] Zhang B, Li Y. Research progress of the antidepressants targeting the glutamate receptors[J]. Chin Pharmacol Bull,2014,30(9):1197-2000.
[2] Luszczki J J, Wojda E, Andres-Mach M, et al. Anticonvulsant and acute neurotoxic effects of imperatorin, osthole and valproate in the maximal electroshock seizure and chimney tests in mice: a comparative study[J]. Epilepsy Res,2009, 85(2-3): 293-9.
[3] 郑莉明,史亚飞,吴皓萌,等.中枢5-HT能系统在早发性抑郁中的作用研究[J].中国药理学通报,2015,31(1):19-23.
[3] Zheng L M, Shi Y F, Wu H M, et al. Research on effect of central 5-HTergic system in early-onset depression[J]. Chin Pharmacol Bull, 2015,31(1):19-23.
[4] 陈红霞,张黎明,薛瑞,等.以5-HT1A受体为靶标的抗抑郁药物研究进展[J]. 军事医学,2013,37(8):624-30.
[4] Chen H X, Zhang L M, Xue R, et al. Progress of antidepressant drugs based on 5-HT1A receptor as a new target[J]. Milit Med Sci,2013,37(8):624-30.
[5] Sharp T, Cowen P J. 5-HT and depression: is the glass half-full[J]. Curr Opin Pharmacol,2011,11(1):45-51.
[6] Kiryanova V, Meunier S J, Dyck R H. Behavioural outcomes of adult female offspring following maternal stress and perinatal fluoxetine exposure[J]. Behav Brain Res,2017,331(7):84-91.
[7] Budzynska B, Boguszewska-Czubara A, Kruk-Slomka M, et al. Effects of imperatorin on scopolamine-induced cognitive impairment and oxidative stress in mice[J]. Psychopharmacology,2015, 232(5): 931-42.
[8] Shi M M, Piao J H, Xu X L, et al. Chinese medicines with sedative-hypnotic effects and their active components[J]. Sleep Med Rev,2016, 29(3):108-18.
[9] Wang S S, Mu R H, Li C F, et al. MicroRNA-124 targets glucocorticoid receptor and is involved in depression-like behaviors[J]. Prog Neuropsychopharmacology Biol Psychiatry,2017,79(ptB):417-25.
[10] Fatima M, Srivastav S, Mondal A C. Prenatal stress and depression associated neuronal development in neonates[J]. Int J Dev Neurosci,2017,60:1-7.
[11] Cao Y J, He X, Wang N, et al. Effects of imperatorin, the active component from Radix Angelicae(Baizhi), on the blood pressure and oxidative stress in 2K,1C hypertensive rats[J]. Phytomedicine, 2013, 20(12): 1048-54.
[12] Han X, Wu H, Yin P, et al. Electroacupuncture restores hippocampal synaptic plasticity via modulation of 5-HT receptors in a rat model of depression[J]. Brain Res Bull, 2018,139:256-62.
[13] ?uszczki J J, Andres-Mach M, Gleńsk M, et al. Anticonvulsant effects of four linear furanocoumarins, bergapten, imperatorin, oxypeucedanin, and xanthotoxin, in the mouse maximal electroshock-induced seizure model: a comparative study[J]. Pharmacol Rep, 2010,62(6): 1231-6.
[14] Wang S J, Lin T Y, Lu C W, et al. Osthole and imperatorin, the active constituents of Cnidium monnieri(L.) Cusson, facilitate glutamate release from rat hippocampal nerve terminals[J]. Neurochem Int, 2008, 53(6-8): 416-23.