嘌呤核苷酸补偿对海洛因依赖大鼠脑组织中 5-HT及5-HIAA 含量的影响及其机制

J4 ›› 2009, Vol. 35 ›› Issue (6): 1024-1028.

嘌呤核苷酸补偿对海洛因依赖大鼠脑组织中 5-HT及5-HIAA 含量的影响及其机制

李鸿梅, 何海涛, 李昆, 刘剑凯, 洪敏

(吉林大学基础医学院生物化学与分子生物学教研室| 吉林长春 130021)

收稿日期:2009-06-03 出版日期:2009-11-28 发布日期:2009-11-28
通讯作者: 洪敏 E-mail:Tel：0431-85619757，E-mail：hongmin1945@yahoo.com.cn
作者简介:李鸿梅(1975-)|女|黑龙江省齐齐哈尔市人|在读医学博士|主要从事阿片作用机制的研究。
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)

Effects of purine nucleotides compensation on contents of 5-HT and5-HIAA in heroin dependent rats and their mechanisms

LI Hong-Mei, HE Hai-tao, LI Kun, LIU Jian-Kai, HONG Min

（Department of Biochemistry and Molecular Biology|School of Basic Medical Sciences|Jilin University|Changchun 130021|China）

Received:2009-06-03 Online:2009-11-28 Published:2009-11-28

摘要/Abstract

摘要：

目的：研究嘌呤核苷酸补偿对海洛因依赖大鼠的戒断症状及脑组织中 5-羟色胺（5-HT）及 5-羟吲哚乙酸（5-HIAA）含量的影响及其作用机制。方法：剂量递增腹腔注射海洛因，建立海洛因依赖大鼠模型，110 只正常雄性 Wistar 大鼠随机分为对照组（C）、海洛因组（H）、海洛因补偿 AMP + GMP 组（HAG）、海洛因补偿 AMP 组（HA）、海洛因补偿 GMP 组（HG），每组 22只。应用荧光分光光度法测定大鼠脑组织中5-HT和 5-HIAA 的含量，ELISA 法测定大鼠脑组织中色氨酸羟化酶（TPH）的含量，免疫组化法检测脑组织中 TPH 蛋白的表达，每组中有 8 只鼠于第 10 天第 1 次给药后 4 h 观察戒断症状，每组中有4只鼠用于免疫组化。结果：与 H 组比较，HAG、HA 及 HG 组大鼠的咀嚼、齿颤及睑下垂次数均明显减少 (P<0.05)。与 C 组比较， H 组大鼠脑组织中 5-HT 和 5-HIAA 含量显著下降 (P<0.05)；与 H 组比较， HAG、HA 和 HG 组大鼠脑组织中 5-HT 和 5-HIAA 含量均有所升高 (P<0.05)。与 C 组比较，H 组大鼠脑组织中 TPH 含量显著下降 (P<0.05)；与 H 组比较，HAG、HA 和 HG 组大鼠脑组织中 TPH 含量均有所升高 (P<0.05)。与 C 组比较，H 组大鼠脑组织中 THP 表达的阳性细胞计数明显减少(P<0.05)；与 H 组比较，HAG、HA 及 HG 组大鼠脑组织中 THP 表达的阳性细胞计数有所升高(P<0.05)。结论：嘌呤核苷酸补偿能够减轻海洛因依赖大鼠的戒断症状，并能增加大鼠脑组织中 5-HT 和 TPH 的含量。

关键词: 嘌呤核苷酸；海洛因；5-羟色胺；5-羟吲哚乙酸；色氨酸羟化酶

Abstract:

To investigate the effects of purine nucleotides compensation on the withdrawal symptoms，contents of 5-hydroxytryptamine（5-HT），5-hydroxyindoleaceticacid （5-HIAA）and their potential mechanisims.Methods
Rats were administered with heroin by intraperitoneal injection with increasing dose to develop addiction models．One hundred and ten male Wistar rats were divided into five groups：control group (C)，heroin group (H)，heroin plus purine mononucleotides (AMP+GMP，equal mole mixture) group (HAG)，heroin plus adenosine monophosphate (AMP) group (HA)，heroin plus guanosine monophosphate (GMP) group (HG).The contents of 5-HT and 5-HIAA were analyzed by fluorospectrophotometry.The content of tryptophan hydroxylase (TPH) was detected by ELISA. The expression of TPH protein was detected by immnunohistochemistry.Eight rats from each group were used for the observation of acute withdrawal symptoms induced by naloxone at 4 h after drug administration on the 10 th day, four rats from each group were used for immunohistochemistry.
Results Withdrawal symptoms were alleviated in HAG，HA and HG groups (P<0.05). The contents of 5-HT and 5-HIAA in H group were significantly decreased compared with C group (P<0.05).While in HAG，HA and HG groups，the contents of 5-HT and 5-HIAA were increased when compared with H group (P<0.05).The TPH content was decreased in H group when compared with C group (P<0.05)； in HAG，HA and HG groups，the TPH contents were increased when compared with H group (P<0.05)；the expression of TPH protein was decreased in H group when compared with C group (P<0.05)，and it was increased in HAG，HA and HG groups when compared with H group (P<0.05).
Conclusion Purine nucleotides can partly alleviate withdrawal symptoms and increase the contents of 5-HT and TPH in heroin dependent rats.

Key words: purine nucleotides；heroin；serotonin；5-hydroxyindoleacetic acid；tryptophan hydroxylase

中图分类号:

R996

李鸿梅, 何海涛, 李昆, 刘剑凯, 洪敏. 嘌呤核苷酸补偿对海洛因依赖大鼠脑组织中 5-HT及5-HIAA 含量的影响及其机制[J]. J4, 2009, 35(6): 1024-1028.

LI Hong-Mei, HE Hai-tao, LI Kun, LIU Jian-Kai, HONG Min. Effects of purine nucleotides compensation on contents of 5-HT and5-HIAA in heroin dependent rats and their mechanisms[J]. J4, 2009, 35(6): 1024-1028.

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