三草安神方对抑郁症失眠大鼠海马凋亡相关蛋白表达的调节作用
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摘要
目的:观察三草安神方对抑郁症失眠大鼠海马凋亡相关蛋白表达的影响。方法:制备抑郁症失眠模型,将大鼠随机分为空白组、模型组、西药组和三草安神方组。三草安神方组给予水煎三草安神方制成的药液(7.8g·kg~(-1)·d~(-1),1mL/100g),西药组给予盐酸帕罗西汀片和奥氮平制成的溶液(盐酸帕罗西汀片:10mg·kg~(-1)·d~(-1),奥氮平:3mg·kg~(-1)·d~(-1),1mL/100g),空白组和模型组给予等体积0.9%氯化钠溶液,连续灌胃14d,尼氏染色观察大鼠海马病理形态变化,RT-PCR和Western blot检测各组大鼠海马Caspase-3、Bcl-2 mRNA和蛋白表达水平。结果:模型组大鼠海马齿状回区细胞层次减少,细胞紊乱、变稀、中断,可见大量的尼氏体固缩、深染,且排列不整齐。西药组和三草安神方组大鼠海马齿状回区细胞排列较规则,细胞层次较丰富,有少量的尼氏体固缩、深染。与空白组比较,模型组大鼠海马中Caspase-3 mRNA和蛋白表达水平显著升高(P<0.01),而Bcl-2m RNA和蛋白表达水平显著降低(P<0.01)。与模型组比较,西药组和三草安神方组大鼠海马中Caspase-3 mRNA和蛋白表达水平显著降低(P<0.01,P<0.05),而Bcl-2 mRNA和蛋白表达水平显著升高(P<0.01,P<0.05)。结论:三草安神方有助于改善抑郁症失眠大鼠海马神经元的损伤,其作用可能与调节大鼠海马凋亡相关蛋白的表达有关。
Objective: To observe the effects of Sancao Anshen Prescription on the expression of apoptosis-related proteins in hippocampus of depressed insomnia rats. Methods: To prepare the insomnia model of depression, the rats were randomly divided into blank group, model group, western medicine group and Sancao Anshen Prescription group. The Sancao Anshen Prescription group was given the medicine made of Sancao Anshen Prescription(7.8 g·kg~(-1)·d~(-1), 1 mL/100 g), western medicine group was given olanzapine solution made of Paroxetine Hydrochloride Tablets(Paroxetine Hydrochloride Tablets:10 mg·kg~(-1)·d~(-1), olanzapine: 3 mg·kg~(-1)·d~(-1), 1 mL/100 g). Blank group and model group were given the same volume of 0.9% sodium chloride solution by gavage for 14 days. Nissle staining was used to observe the pathological changes of hippocampus in rats,the mRNA and protein expressions of Caspase-3 and Bcl-2 in hippocampus of rats were detected by RT-PCR and Western bolt. Results: The cell levels of the hippocampal dentate gyrus in the model group were decreased, the cells were disordered,thinned and disrupted, and a large number of Nissle bodies were condensed, deeply dyed, and arranged neatly. The cells of the hippocampal dentate gyrus in the western medicine group and the Sancao Anshen Prescription group were more regular, and the cell level was more abundant, with a small amount of Nissle body nitholar solids and deep dyeing. Compared with the blank group,the expression level of Caspase-3 mRNA and protein in the hippocampus of the rats in model group was significantly increased(P<0.01), while the expression level of Bcl-2 mRNA and protein was significantly decreased(P<0.01). Compared with the model group, the expression of Caspase-3 mRNA and protein in the hippocampus of the western medicine group and the Sancao Anshen Prescription group were significantly decreased(P<0.01, P<0.05), while the expression of Bcl-2 mRNA and protein was significantly increased(P<0.01, P<0.05). Conclusion: Sancao Anshen Prescription can improve the damage of hippocampal neurons in depressed rats, and its effect may be related to the regulation of apoptosis-related protein expression in hippocampus of rats.
Objective: To observe the effects of Sancao Anshen Prescription on the expression of apoptosis-related proteins in hippocampus of depressed insomnia rats. Methods: To prepare the insomnia model of depression, the rats were randomly divided into blank group, model group, western medicine group and Sancao Anshen Prescription group. The Sancao Anshen Prescription group was given the medicine made of Sancao Anshen Prescription(7.8 g·kg~(-1)·d~(-1), 1 mL/100 g), western medicine group was given olanzapine solution made of Paroxetine Hydrochloride Tablets(Paroxetine Hydrochloride Tablets:10 mg·kg~(-1)·d~(-1), olanzapine: 3 mg·kg~(-1)·d~(-1), 1 mL/100 g). Blank group and model group were given the same volume of 0.9% sodium chloride solution by gavage for 14 days. Nissle staining was used to observe the pathological changes of hippocampus in rats,the mRNA and protein expressions of Caspase-3 and Bcl-2 in hippocampus of rats were detected by RT-PCR and Western bolt. Results: The cell levels of the hippocampal dentate gyrus in the model group were decreased, the cells were disordered,thinned and disrupted, and a large number of Nissle bodies were condensed, deeply dyed, and arranged neatly. The cells of the hippocampal dentate gyrus in the western medicine group and the Sancao Anshen Prescription group were more regular, and the cell level was more abundant, with a small amount of Nissle body nitholar solids and deep dyeing. Compared with the blank group,the expression level of Caspase-3 mRNA and protein in the hippocampus of the rats in model group was significantly increased(P<0.01), while the expression level of Bcl-2 mRNA and protein was significantly decreased(P<0.01). Compared with the model group, the expression of Caspase-3 mRNA and protein in the hippocampus of the western medicine group and the Sancao Anshen Prescription group were significantly decreased(P<0.01, P<0.05), while the expression of Bcl-2 mRNA and protein was significantly increased(P<0.01, P<0.05). Conclusion: Sancao Anshen Prescription can improve the damage of hippocampal neurons in depressed rats, and its effect may be related to the regulation of apoptosis-related protein expression in hippocampus of rats.
引文
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[13]傅锦华,刘勇,王清勇,等.舒肝解郁胶囊对抑郁模型大鼠海马神经元凋亡及脑组织Caspase-3蛋白表达的影响.中南大学学报(医学版),2012,37(12):1198-1204
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[2]Xie H,Yung W H.Chronic intermittent hypoxia-induced deficits in synaptic plasticity and neurocognitive functions:A role for brain-derived neurotrophic factor.Chinese Journal of Pharmacology,2012,33(1):5-10
[3]彭成国,王高华,张新风,等.帕罗西汀合并小剂量奥氮平治疗抑郁症伴失眠患者的对照研究.海南医学院学报,2014,20(9):1289-1290
[4]王彦芳,杜巧荣,李素萍,等.伴发睡眠障碍首发抑郁症认知功能损害及影响因素分析.中国神经精神疾病杂志,2015,41(2):71-75
[5]龙清华,赵宾宾,王平.中药三草安神方对抑郁症失眠大鼠行为学及神经递质含量的影响.时珍国医国药,2018,29(1):64-66
[6]龙清华,赵宾宾,王平.三草安神方对抑郁症失眠大鼠学习记忆力及神经递质受体表达的影响.中华中医药杂志,2018,33(8):3547-3550
[7]彭成国,王高华,张新风,等.帕罗西汀合并小剂量奥氮平治疗抑郁症伴失眠患者的对照研究.海南医学院学报,2014,20(9):1289-1290
[8]Lin J R,Fang S C,Tang S S,et al.Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice.Chinese Journal of Pharmacology,2017,38(4):1-11
[9]樊凌,吕爱平,符文彬,等.针刺对抑郁症大鼠海马5-HT、NE、BDNF水平和神经元细胞凋亡相关基因表达的影响.中华中医药杂志,2016,31(8):3204-3207
[10]Villarreal D,Derrick B I.Prenatal morphine exposure attenuates the maintenance of late LTP in lateral perforant path projections to the dentate gyrus and the CA3 region in vivo.Journal of Neurophysiology,2008,99(3):1235-1242
[11]宋晓灵,张芳,曹莉莎,等.氟西汀对抑郁大鼠模型海马CA1区、CA3区及齿状回区神经生长因子表达的影响.武汉大学学报(医学版),2015,36(2):185-188
[12]Yang S,Wang L,Kong Q.Depression of focal adhesion kinase induces apoptosis in rat osteosarcoma OSR-6 cells in a caspase-dependent pathway.Cell Biochemistry&Biophysics,2014,70(2):765-770
[13]傅锦华,刘勇,王清勇,等.舒肝解郁胶囊对抑郁模型大鼠海马神经元凋亡及脑组织Caspase-3蛋白表达的影响.中南大学学报(医学版),2012,37(12):1198-1204
[14]Guan L,Jia N,Zhao X,et al.The involvement of ERK/CREB/Bcl-2 in depression-like behavior in prenatally stressed offspring rats.Brain Research Bulletin,2013,99(5):1-8