J4 ›› 2010, Vol. 36 ›› Issue (1): 123-126.

• 基础研究 • 上一篇    下一篇

嘌呤核苷酸补偿对海洛因依赖大鼠脑组织中DA和NE水平的影响及其机制

 何海涛, 李鸿梅, 李昆, 崔佳乐, 刘剑凯, 洪敏   

  1. 吉林大学基础医学院生物化学教研室,吉林 长春 130021
  • 收稿日期:2009-05-22 出版日期:2010-01-28 发布日期:2010-01-28
  • 通讯作者: 洪 敏(Tel:0431-85619757,E-mail:hongmin1945@yahoo.com.cn) E-mail:hongmin1945@yahoo.com.cn
  • 作者简介:何海涛 (1981-)|女|河北省石家庄市人|在读理学博士,主要从事阿片对神经系统影响的研究。
  • 基金资助:

    吉林省科技厅科技发展计划项目资助课题(20080435-2);吉林大学重大重点项目发展启动基金资助课题(200602037)

Effect of purine nucleotides compensation on levels of DA and |NE in brain tissue and its potential mechanisms in heroin dependent rats

 HE Hai-Tao, LI Hong-Mei, LI Kun, CUI Jia-Ye, LIU Jian-Kai, HONG Min   

  1. Department of Biochemistry,School of Basic Medical Sciences,Jilin University,Changchun 130021,China
  • Received:2009-05-22 Online:2010-01-28 Published:2010-01-28

摘要:

目的:探讨外源性嘌呤核苷酸补偿对海洛因依赖大鼠脑组织中多巴胺(DA)和去甲肾上腺素(NE)水平以及代谢关键酶的影响,探索嘌呤核苷酸治疗药物依赖的可能性。方法:65只雄性Wistar大鼠随机分为对照组(C)、海洛因组(H)、海洛因+嘌呤核苷酸组(HAG)、海洛因+腺嘌呤核苷酸组(HA)、海洛因+鸟嘌呤核苷酸组(HG),每组13只。荧光分光光度计法检测各组大鼠中脑组织中DA和NE水平,ELISA试剂盒检测酪氨酸羟化酶(TH)水平,实时定量PCR法检测TH的表达。电镜下观察大鼠VTA区神经结构的形态变化。结果:与C组比较, H组DA、NE、TH水平和TH表达水平降低(P<0.05)。与H组比较,HAG组DA、NE、TH水平升高(P<0.05),HA组TH水平升高(P<0.05),HG组TH、NE水平升高(P<0.05)。与C组比较,H组TH基因表达降低;与H组比较,HAG、HA及HG组中TH基因表达水平升高(P<0.05)。电镜下H组出现神经毡水肿及髓鞘脱落现象,HAG、HA和HG组常染色体稍有增多,超微结构损伤都较H组减轻。 结论:嘌呤核苷酸补偿能提高大鼠脑组织中DA和NE的水平,能够减轻海洛因对大鼠造成的损伤,提示嘌呤核苷酸治疗药物依赖具有可行性。

关键词: 嘌呤核苷酸类;海洛因;多巴胺;去甲肾上腺素;酪氨酸羟化酶

Abstract:

Abstract:Objective  To investigate the effect of purine nucleotides compensation on the levels of dopamine (DA) and norepinephrine( NE) in brain tissue in rats and its possible mechanisims for heroin addiction. Methods Sixty five male Wistar rats were randomly divided into five groups (n=13):control group(C),heroin group (H),heroin plus AMP and GMP group (HAG),heroin plus AMP group (HA),heroin plus GMP group (HG).The levels of DA and NE in brain tissue were examined by fluorospectrophotometry.The activity of tyrosine hydroxylase (TH) in brain tissue was detected by ELISA.The TH expression was determined by real-time PCR. The ultrastructure changes of VTA were observed by transmission electron microscopy.Results The levels of DA,NE,TH and the expression level of TH in brain tissue in H group were significantly decreased compared with C group (P< 0.05).While in HAG group,the DA,NE and TH levels were increased when compared with H group (P< 0.05). In HA group,the TH level was increased when compared with H group (P< 0.05).In HAG,HA and HG groups,the  TH expression levels  were increased when compared with H group (P< 0.05).Under electron microscope,the impairment in HAG,HA,and HG groups was less than that in H group.Neuropil swelled and medullary sheath was detached in H group.Autosome was increased in HAG,HA and HG groups.Conclusion Purine nucleotides compensation can partly alleviate the impairment which caused by heroin and increase the contents of DA and NE in brain tissue in heroin dependent rats.

Key words: purine nucleotides;heroin;dopamine;norepinephrine;tyrosine hydroxylase

中图分类号: 

  • R996