人参皂苷对创伤后应激障碍大鼠海马神经元的保护作用机制研究
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摘要
目的探讨人参皂苷对创伤后应激障碍(PTSD)大鼠海马神经元的保护作用及可能的作用机制。方法将Wistar大鼠分为3组,空白对照组、PTSD模型组及人参皂苷治疗组,使用Tunel染色观察神经元凋亡情况,测定大鼠海马神经元皮质醇(cortisol)、5-羟色胺(5-HT)、肿瘤坏死因子-ɑ(TNF-α)、白介素-6(IL-6)含量,并分别测定3组的旷场实验、高架十字迷宫实验、Morris水迷宫实验行为学改变情况。结果检测结果显示:空白对照组、PTSD模型组与人参皂苷治疗组5-HT为(1.87±0.47)、(0.36±0.15)、(0.98±0.33)ng/g,TNF-α为(1.27±0.13)、(10.22±0.32)、(5.39±0.27)pg/mL,IL-6为(2.25±0.27)、(14.76±1.12)、(8.96±0.34)pg/mL,皮质醇为(4.33±0.61)、(1.83±0.19)、(3.81±0.42)μg/L,神经元的凋亡率分别为(4.39±0.96)%、(68.35±5.97)%、(39.48±4.15)%,组间差异均有统计学意义(均P<0.05),人参皂苷治疗组行为学功能改善。结论人参皂苷对PTSD大鼠海马神经元具有保护作用,其作用机制可能主要通过调节下丘脑-垂体-肾上腺素皮质轴(HPA轴)及降低炎性反应而获得。
Objective To observe protective effect of Ginsenoside on neurons in rats with posttraumatic stress disorder(PTSD)and the related mechanism.Methods Wistar rats were randomly divided into three groups:the normal control group,PTSD model group,Ginsenoside treatment group.Tunel staining was used to observe the apoptosis of rat hippocampal neurons.Cortisol,5-hydroxytryptamine(5-HT),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)were detected.Moreover behavioral evaluation was performed in open field test,elevated plus maze and Morris water maze.Results In the normal control group,PTSD model group and Ginsenoside treatment group,the concentration of 5-HT was[(1.87±0.47),(0.36±0.15),(0.98±0.33)ng/g];the concentration of TNF-α[(1.27±0.13),(10.22±0.32),(5.39±0.27)pg/mL];the concentration of IL-6[(2.25±0.27),(14.76±1.12),(8.96±0.34)pg/mL],and the concentration of cortisol[(4.33±0.61),(1.83±0.19),(3.81±0.42)μg/L].Apoptosis rates of the three groups were(4.39±0.96)%,(68.35±5.97)%,and(39.48±4.15)%(all P<0.05).Behavioral function was improved.Conclusion Ginsenoside may play a neuroprotective role in hippocampus of PTSD rats by regulation of the HPA axis and reduction of inflammatory response.
Objective To observe protective effect of Ginsenoside on neurons in rats with posttraumatic stress disorder(PTSD)and the related mechanism.Methods Wistar rats were randomly divided into three groups:the normal control group,PTSD model group,Ginsenoside treatment group.Tunel staining was used to observe the apoptosis of rat hippocampal neurons.Cortisol,5-hydroxytryptamine(5-HT),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)were detected.Moreover behavioral evaluation was performed in open field test,elevated plus maze and Morris water maze.Results In the normal control group,PTSD model group and Ginsenoside treatment group,the concentration of 5-HT was[(1.87±0.47),(0.36±0.15),(0.98±0.33)ng/g];the concentration of TNF-α[(1.27±0.13),(10.22±0.32),(5.39±0.27)pg/mL];the concentration of IL-6[(2.25±0.27),(14.76±1.12),(8.96±0.34)pg/mL],and the concentration of cortisol[(4.33±0.61),(1.83±0.19),(3.81±0.42)μg/L].Apoptosis rates of the three groups were(4.39±0.96)%,(68.35±5.97)%,and(39.48±4.15)%(all P<0.05).Behavioral function was improved.Conclusion Ginsenoside may play a neuroprotective role in hippocampus of PTSD rats by regulation of the HPA axis and reduction of inflammatory response.
引文
[1]段发亮,王孟阳,何主强,等.吲哚胺2,3-双加氧酶在创伤后应激障碍大鼠海马中的表达变化与作用[J].华中科技大学学报:医学版,2016,45(4):385-388.
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[6]Moeller D R,Duffy J M,Goolsby A M,et al.Use of a removable mandibular neuroprosthesis for the reduction of posttraumatic stress disorder(PTSD)and mild traumatic brain injury/PTSD/associated nightmares,headaches,and sleep disturbances[J].Spec Oper Med,2014,14(3):64-73.
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[9]刘丽琴,罗艳,张瑞睿,等.人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响[J].中国中药杂志,2011,36(10):1342-1347.
[10]王卫霞,王谦.人参皂苷的免疫调节作用及其应用[J].中华中医药杂志,2009,20(4):234-236.
[11]Hinz B,Brune K.Paracetamol and cyclooxygenase inhibition:is there a cause for concern[J].Ann Rheum Dis,2012,71(1):20-25.
[12]Said R S,Badr A M,Nada A S,et al.Sodium selenite treatment restores long-lasting ovarian damage induced by irradiation in rats:impact on oxidative stress and apoptosis[J].Reprod Toxicol,2014,43(5):85-93.
[13]Nury T,Zarrouk A,Vejux A,et al.Induction of oxiapoptophagy,a mixed mode of cell death associated with oxidative stress,apoptosis and autophagy,on 7-ketocholesterol-treated158N murine oligodendrocytes:impairment byα-tocopherol[J].Biochem Biophys Res Commun,2014,446(3):714-719.
[14]Puetz T W,Youngstedt S D,Herring M P.Effects of pharmacotherapy on combat-related ptsd,anxiety,and depression:a systematic review and meta-regression analysis[J].PLoS One,2015,10(5):529-532.
[15]冯毅,赵自明,陈媛,等.人参皂苷Re对运动性疲劳模型大鼠MDA含量和SOD活性的影响.[J].中药新药与临床药理,2009,20(6):542-544.
[16]庄鹏伟,张艳军,庞坦.人参皂苷Rg1促进体外培养神经干细胞增殖的研究[J].中国中药杂志,2009,34(4):443-446.
[2]何主强,殷莉,黄珊珊.环氧化酶-2及细胞因子在创伤后应激障碍患者中的表达变化及意义[J].实用医学,2015,31(19):3166-3168.
[3]Pietrzak R H,Goldstein R B,Southwick S M,et al.Psychiatric comorbidity of full and partial posttraumatic stress disorder among older adults in the United States:results from wave 2of the National Epidemiologic Survey on Alcohol and Related Conditions[J].Am J Geriatr Psychiatry,2012,20(5):380-390.
[4]Cohen H,Kaplan Z,Koresh O,et al.Early post-stressor intervention with propranolol is ineffective in preventing posttraumatic stress responses in an animal model for PTSD[J].Eur Neuropsychopharmacol,2011,21(3):230-240.
[5]Thomas C,Eric E,Rachel Y.Biomarkers for combat-related PTSD:focus on molecular networks from high-dimensional data[J].Eur J Psychotraumatol,2014,5(7):1-3.
[6]Moeller D R,Duffy J M,Goolsby A M,et al.Use of a removable mandibular neuroprosthesis for the reduction of posttraumatic stress disorder(PTSD)and mild traumatic brain injury/PTSD/associated nightmares,headaches,and sleep disturbances[J].Spec Oper Med,2014,14(3):64-73.
[7]Koek R J,Langevin J P,Krahl S E,et al.Deep brain stimulation of the basolateral amygdala for treatment-refractory combat post-traumatic stress disorder(PTSD):study protocol for apilot randomized controlled trial with blinded,staggered onset of stimulation[J].Trials,2014,15(5):356-358.
[8]Kousha M,Mehdizadeh T S.Normative life events and PTSD in children:how easy stress can affect children’s brain[J].Acta Med Iran,2013,51(1):47-51.
[9]刘丽琴,罗艳,张瑞睿,等.人参皂苷对慢性应激抑郁模型大鼠行为学及HPA轴、BDNF的影响[J].中国中药杂志,2011,36(10):1342-1347.
[10]王卫霞,王谦.人参皂苷的免疫调节作用及其应用[J].中华中医药杂志,2009,20(4):234-236.
[11]Hinz B,Brune K.Paracetamol and cyclooxygenase inhibition:is there a cause for concern[J].Ann Rheum Dis,2012,71(1):20-25.
[12]Said R S,Badr A M,Nada A S,et al.Sodium selenite treatment restores long-lasting ovarian damage induced by irradiation in rats:impact on oxidative stress and apoptosis[J].Reprod Toxicol,2014,43(5):85-93.
[13]Nury T,Zarrouk A,Vejux A,et al.Induction of oxiapoptophagy,a mixed mode of cell death associated with oxidative stress,apoptosis and autophagy,on 7-ketocholesterol-treated158N murine oligodendrocytes:impairment byα-tocopherol[J].Biochem Biophys Res Commun,2014,446(3):714-719.
[14]Puetz T W,Youngstedt S D,Herring M P.Effects of pharmacotherapy on combat-related ptsd,anxiety,and depression:a systematic review and meta-regression analysis[J].PLoS One,2015,10(5):529-532.
[15]冯毅,赵自明,陈媛,等.人参皂苷Re对运动性疲劳模型大鼠MDA含量和SOD活性的影响.[J].中药新药与临床药理,2009,20(6):542-544.
[16]庄鹏伟,张艳军,庞坦.人参皂苷Rg1促进体外培养神经干细胞增殖的研究[J].中国中药杂志,2009,34(4):443-446.