中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (1): 140-145.doi: 10.3969/j.issn.2095-4344.2017.01.025

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

神经干细胞移植联合电针刺激对慢性应激抑郁模型大鼠行为学的影响

米 琨1,郭 强2,孙振卿2,王海波2   

  1. 1河北省第六人民医院情感障碍二科,河北省保定市 071000;2河北大学附属医院胸外科,河北省保定市 071000
  • 出版日期:2017-01-08 发布日期:2017-03-15
  • 通讯作者: 郭强,主任医师,河北大学附属医院胸外科,河北省保定市 071000
  • 作者简介:米琨,女,1981年生,河北省保定市人,汉族,2006年河北医科大学毕业,主治医师,主要从事精神卫生疾病的临床与基础研究。

Combined effects of neural stem cell transplantation and electroacupuncture on the behaviors of chronic stress-induced depression rats

Mi Kun1, Guo Qiang2, Sun Zhen-qing2, Wang Hai-bo2   

  1. 1Second Department of Affective Disorder, Sixth People's Hospital of Hebei Province, Baoding 071000, Hebei Province, China; 2Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
  • Online:2017-01-08 Published:2017-03-15
  • Contact: Guo Qiang, Chief physician, Department of Thoracic Surgery, Affiliated Hospital of Hebei University, Baoding 071000, Hebei Province, China
  • About author:Mi Kun, Attending physician, Second Department of Affective Disorder, Sixth People's Hospital of Hebei Province, Baoding 071000, Hebei Province, China

摘要:

文章快速阅读: 

 

文题释义:
Caspase家族:在介导细胞凋亡的过程中起着非常重要的作用,其中Caspase-3为关键的执行分子,它在凋亡信号传导的许多途径中发挥功能。Caspase-3正常以酶原的形式存在于胞浆中,在凋亡的早期阶段,它被激活,活化的Caspase-3由两个大亚基和两个小亚基组成,裂解相应的胞浆胞核底物,最终导致细胞凋亡。在细胞凋亡的晚期和死亡细胞,Caspase-3的活性明显下降。

电针刺激:针刺腧穴得气后,在针上通以接近人体生物电的微量电流以防治疾病的一种疗法。优点:①针与电两种刺激相结合,可提高疗效;②能比较正确地掌握刺激参数;③代替手法运针,节省人力。

 

 

摘要

背景:电针刺激及神经干细胞移植对慢性应激抑郁均有一定治疗效果,二者是否有协同作用有待进一步研究。

目的:探讨神经干细胞尾静脉移植联合电针刺激对慢性应激抑郁模型大鼠行为学的影响。

方法:63只雄性SPF级SD大鼠随机取15只不予任何处理为正常组,余48只应用孤养联合慢性不可预见性温和应激方法建立大鼠抑郁模型,剔除造模不成功的大鼠3只,将造模成功的45只大鼠随机分为3组:模型组(n=15,不给予任何处理)、神经干细胞组(n=15,尾静脉注射1 mL神经干细胞悬液,细胞数3×106个)、电针刺激联合神经干细胞组(n=15,尾静脉注射1 mL神经干细胞悬液+隔日一次1 h电针刺激,持续1周)。采用蔗糖水消耗实验和旷场实验评估大鼠行为学的改变,荧光显微镜观察CM-Dil标记的神经干细胞的存活和分布情况,TUNEL法检测神经细胞凋亡情况,RT-PCR、Western blot检测海马CA3区Caspase-3、Bcl-2基因和蛋白的表达。
结果与结论:①与正常组相比,模型组大鼠体质量、蔗糖水偏嗜度、旷场实验得分明显偏低,大鼠海马CA3区Caspase-3基因和蛋白表达显著升高(P < 0.05);Bcl-2基因和蛋白表达显著降低(P < 0.05),可见较多神经元凋亡(P < 0.05);②与模型组相比,神经干细胞组和电针刺激联合神经干细胞组大鼠体质量、蔗糖水偏嗜度、旷场实验得分明显增加,海马CA3区Caspase-3基因和蛋白表达显著降低(P < 0.05),Bcl-2基因和蛋白表达显著升高(P < 0.05)。电针刺激联合神经干细胞组各指标改善较神经干细胞组明显(P < 0.05),荧光显微镜观察电针刺激干预神经干细胞组可见较多CM-Dil阳性细胞;③结果表明,移植神经干细胞可以改善慢性应激抑郁模型大鼠的抑郁行为,电针刺激可能通过降低Caspase-3表达和升高Bcl-2表达,起到提高移植神经干细胞存活率的作用。

 

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程
ORCID:
0000-0001-6518-3854(米琨)

关键词: 干细胞, 移植, 抑郁, 电针刺激, 神经干细胞, 细胞凋亡, 大鼠

Abstract:

BACKGROUND: Both electroacupuncture and neural stem cell transplantation have certain therapeutic effects on chronic stress depression, but their synergistic effects remain unclear.
OBJECTIVE: To explore the effect of electroacupuncture intervention combined with neural stem cell transplantation via tail vein on the behaviors of chronic stress-induced depression rats.
METHODS: Fifteen of 63 rats were randomly selected as normal group, and the other 48 rats were fed individually and underwent chronic unpredictable mild stress stimulation to make rat models of depression. Except for three unsuccessful models, 45 successful models were randomly assigned into model (no intervention), neural stem cell (injection of 1 mL neural stem cell suspension (3×106) via the tail vein), or combined treatment group (injection of 1 mL neural stem cell suspension (3×106) via the tail vein+1-hour electroacupuncture every other day for consecutive 1 week) (n=15/group). The behavior ability of rats was assessed through sucrose preference test and open-field test. The survival, distribution and apoptosis of neural stem cells were assessed by CM-Dil labeling and TUNEL assay, respectively. The expression of Caspase-3 and Bcl-2 in the hippocampal CA3 region was assessed by RT-PCR and western blot assay.
RESULTS AND CONCLUSION: Compared with the normal group, model group rats exhibited lower body mass, lower scores on the sucrose preference test and open-field test, higher Caspase-3 mRNA and protein expressions (P < 0.05), lower Bcl-2 protein and mRNA expressions (P < 0.05) and more apoptotic neurons (P < 0.05). Compared with the model group, rats in the neural stem cell group and combined treatment group had significant increases in the body mass and scores on the sucrose preference test and open-field test as well as exhibited significantly decreased Caspase-3 mRNA and protein expressions (P < 0.05) and increased Bcl-2 protein and mRNA expressions (P < 0.05). These indicators were improved better in the combined treatment group than the neural stem cell group (P < 0.05). Under the fluorescence microscope, there were more CM-Dil-positive cells in the combined treatment group than the neural stem cell group. To conclude, neural stem cell transplantation can improve depressive behaviors in rats with chronic stress-induced depression, and electroacupuncture can elevate the survival rate of transplanted neural stem cells by reducing Caspase-3 and increasing Bcl-2 expression.

 

中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

Key words: Depression, Electroacupuncture, Neural Stem Cells, Tissue Engineering

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