帕罗西汀片对抑郁症大鼠模型抑郁行为的改善效果及相关作用机制分析
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摘要
目的研究帕罗西汀片对抑郁症大鼠模型抑郁行为的改善效果及相关作用机制。方法将60只健康雄性SD大鼠随机分为对照组,模型组及实验组,各20只。模型组及实验组以孤养结合慢性轻度不可预见刺激构建抑郁症大鼠模型,对照组则正常饲养。建模期间实验组灌胃帕罗西汀1. 8 mg·kg~(-1),qd,对照组及模型组灌胃等量0. 9%NaCl,均连续给药3周。Open-field实验及Morris水迷宫测试检分别检测大鼠抑郁行为及记忆,学习能力改善情况;免疫组化法检测大鼠海马CA3区脑源性神经营养因子(BDNF),酪氨酸激酶受体B(TrkB)蛋白表达情况。结果对照组,模型组和实验组大鼠自主活动次数分别为(35. 74±9. 38),(6. 57±2. 03),(18. 79±5. 42)次,不动时间分别为(13. 04±7. 12) s,(46. 92±8. 59) s,(20. 51±6. 73) s,定位航行实验第4 d潜伏期分别为(17. 96±2. 15),(24. 68±1. 99),(16. 79±1. 96) s,穿台次数分别为(12. 46±2. 87),(5. 11±2. 34),(9. 36±1. 98)次。对照组,模型组及实验组大鼠海马CA3区BDNF蛋白阳性细胞百分比分别为(58. 46±7. 94)%,(32. 17±8. 01)%,(47. 56±7. 62)%; TrkB蛋白阳性细胞百分比分别为(39. 15±6. 23)%,(18. 07±5. 97)%,(33. 46±5. 47)%,差异均有统计学意义(均P <0. 05)。结论帕罗西汀片可有效改善抑郁症大鼠抑郁症状,提高其学习,记忆能力,其作用机制可能与上调海马CA3区BDNF,TrkB蛋白表达相关。
Objective To explore the improvement effect of paroxetine tablets on the depressive behavior of depression rats model and the related action mechanisms. Methods Sixty healthy male SD rats were divided randomly into control group,model group and test group,20 rats were assigned to each group. Unpredictable chronic mild stress model of depression were established in the model group and test group,while control group was fed normal diet. Subsequently,the test group was treated with 1. 8 mg·kg~(-1) of paroxetine by gastrointestinal administration once daily,while control group and model group were treated with equal amount of 0. 9% NaCl. All rats were treated for 3 weeks. The improvement of depressive behavior,memory and learning ability of rats were measured by Open-field test and Morris water maze test; the expression of brain derived neurotrophic factor( BDNF),tyrosine kinase receptor B( TrkB) protein in hippocampal CA3 area were detected by immunohistochemistry. Results The number of autonomic activity of control group,model group,test group were( 35. 74 ± 9. 38),( 6. 57 ± 2. 03),( 18. 79 ± 5. 42) times,respectively; the motionless time were( 13. 04 ± 7. 12),( 46. 92 ± 8. 59),( 20. 51 ± 6. 73) s,respectively; the latent period of Morris water maze navigation experiment on Day 4 were( 17. 96 ± 2. 15),( 24. 68 ± 1. 99),( 16. 79 ± 1. 96) s,respectively; the number of passes were( 12. 46 ± 2. 87),( 5. 11 ± 2. 34),( 9. 36 ± 1. 98) times,respectively; the percentage of BDNF protein positive cells in hippocampal CA3 area were( 58. 46 ± 7. 94) %,( 32. 17 ± 8. 01) %,( 47. 56 ± 7. 62) %,respectively; the percentage of TrkB protein were( 39. 15 ± 6. 23) %,( 18. 07 ± 5. 97) %,( 33. 46 ± 5. 47) %,respectively. There were significant differences among the groups( P < 0. 05). Conclusion Paroxetine tablets can improve the depressive behavior,enhance the memory and learning ability,and the action mechanism maybe related to the up-regulation of BDNF,TrkB protein expression in hippocampal CA3 area of rats.
Objective To explore the improvement effect of paroxetine tablets on the depressive behavior of depression rats model and the related action mechanisms. Methods Sixty healthy male SD rats were divided randomly into control group,model group and test group,20 rats were assigned to each group. Unpredictable chronic mild stress model of depression were established in the model group and test group,while control group was fed normal diet. Subsequently,the test group was treated with 1. 8 mg·kg~(-1) of paroxetine by gastrointestinal administration once daily,while control group and model group were treated with equal amount of 0. 9% NaCl. All rats were treated for 3 weeks. The improvement of depressive behavior,memory and learning ability of rats were measured by Open-field test and Morris water maze test; the expression of brain derived neurotrophic factor( BDNF),tyrosine kinase receptor B( TrkB) protein in hippocampal CA3 area were detected by immunohistochemistry. Results The number of autonomic activity of control group,model group,test group were( 35. 74 ± 9. 38),( 6. 57 ± 2. 03),( 18. 79 ± 5. 42) times,respectively; the motionless time were( 13. 04 ± 7. 12),( 46. 92 ± 8. 59),( 20. 51 ± 6. 73) s,respectively; the latent period of Morris water maze navigation experiment on Day 4 were( 17. 96 ± 2. 15),( 24. 68 ± 1. 99),( 16. 79 ± 1. 96) s,respectively; the number of passes were( 12. 46 ± 2. 87),( 5. 11 ± 2. 34),( 9. 36 ± 1. 98) times,respectively; the percentage of BDNF protein positive cells in hippocampal CA3 area were( 58. 46 ± 7. 94) %,( 32. 17 ± 8. 01) %,( 47. 56 ± 7. 62) %,respectively; the percentage of TrkB protein were( 39. 15 ± 6. 23) %,( 18. 07 ± 5. 97) %,( 33. 46 ± 5. 47) %,respectively. There were significant differences among the groups( P < 0. 05). Conclusion Paroxetine tablets can improve the depressive behavior,enhance the memory and learning ability,and the action mechanism maybe related to the up-regulation of BDNF,TrkB protein expression in hippocampal CA3 area of rats.
引文
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[3]WILLNER P,TOWELL A,SAMPSON D,et al.Reduction of sucrose preference by chronic unpredictable mild stress,and its restoration by a tricyclic antidepressant[J].Psychopharmacol,1987,93(3):358-364.
[4]孙林,谢忠礼,郭选贤,等.菖郁导痰汤对抑郁大鼠模型额叶5-HT2AR及其mRNA表达的干预[J].中国实验方剂学杂志,2011,17(6):223-224.
[5]林岚燕.ApoE4年龄依赖性增加应激诱导的抑郁样行为的易感性和学习记忆能力的下降[D].福州:福建医科大学,2016.
[6]王若男.舒郁颗粒对慢性不可预见性应激刺激小鼠行为学及脑组织海马区C-FOS蛋白表达的影响[D].长春:长春中医药大学,2017.
[7]ZHOU W,WANG N,YANG C,et al.Ketamine-induced antidepressant effects are associated with AMPA receptors-mediated upregulation of m TOR and BDNF in rat hippocampus and prefrontal cortex[J].Eur Psychiat,2014,29(7):419-423.