地佐环平诱导的精神分裂症发育模型大鼠脑组织去甲肾上腺素、5-羟色胺及代谢产物的浓度变化

摘要/Abstract

摘要： 目的: 通过对地佐环平(MK-801)诱导的精神分裂症(Schizophrenia, SZ)发育和慢性给药模型大鼠脑组织去甲肾上腺素(norepinephrine, NE)和5-羟色胺(5-hydroxytryptamine, 5-HT)及相关代谢产物浓度的比较研究,探讨围产期N-甲基-D-天冬氨酸(N-methyl-D-aspartate, NMDA)受体阻断致SZ的神经生化机制。 方法: 24只新生雄性SD大鼠于出生后 6 d 随机分为SZ发育模型组(MK-801F)、SZ慢性给药模型组(MK-801M)和正常对照组(Control);SZ发育模型大鼠于出生后7～10 d 皮下注射MK-801(0.1 mg/kg,bid),SZ慢性给药模型大鼠于出生后47～60 d 腹腔注射MK-801(0.2 mg/kg,qd),对照组大鼠于相应时段注射 0.9%的生理盐水(Normal saline,NS)。出生后 63 d 取各组大鼠大脑内侧前额叶皮质(medial prefrontal cortex , mPFC)和海马组织并匀浆,以高效液相色谱-库仑阵列电化学法检测组织匀浆中的NE、甲氧基羟基苯乙二醇(Methoxyhydroxyphenylglycol, MHPG)、5-HT和5-羟吲哚乙酸(5-hydroxyindoleacetic acid, 5-HIAA),并计算分析NE和5-HT的利用率。 结果: SZ慢性给药模型大鼠mPFC区NE和5-HT浓度较对照组和SZ发育模型组显著升高(P<0.01 或 0.05),两模型组大鼠mPFC区5-HIAA浓度较对照组显著升高(P<0.01 或 0.05);与对照组和SZ慢性给药模型组比较,SZ发育模型大鼠海马MHPG浓度和MHPG/NE比值显著升高(P<0.05),5-HT和5-HIAA浓度显著降低(P<0.01 或 0.05)。 结论: 围产期MK-801重复处理诱导的SZ发育模型大鼠mPFC区和海马5-HT能递质系统功能减退,海马NE能递质系统功能减退。

关键词: 精神分裂症, 发育, 地佐环平, 去甲肾上腺素, 5-羟色胺

Abstract: AIM: To explore the related neurobiochemistry pathomechanism by the comparison of concentration of norepinephrine (NE), 5-hydroxytryptamine (5-HT) and their metabolites in brain tissue in the schizophrenia (SZ) developmental model rats. METHODS: 24 neonatal male Spragur-Dawley (SD) rats were randomly assigned at the postnatal day 6 to 3 groups: a SZ developmental model group (subcutaneous injection with MK-801 at the postnatal day 7-10, 0.1 mg/kg bid), a chronic medication model group (intraperitoneal injection at the postnatal day 47-60, 0.2 mg/kg,qd) and a normal control group (injection with 0.9% normal saline during the corresponding periods). NE, Methoxyhydr-oxyphenylglycol (MHPG), 5-HT and 5-hydroxyindo-leacetic acid (5-HIAA) of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray Electrochemic detection for high performance liquid chromatogram (HPLC) technique. Meanwhile, the utilization rate of NE and 5-HT was calculated. RESULTS: The NE and 5-HT concentration in the mPFC were significantly increased in SZ chronic medication model group compared with in normal control and SZ developmental model group, respectively (P<0.01 or 0.05); the 5-HIAA concentration in the mPFC were significantly increased in both SZ chronic medication and SZ developmental model group compared with in normal control group, respectively (P<0.01 or 0.05); compared to normal control and SZ chronic medication model group respectively, the MHPG concentration and NE utilization rate were significantly increased (P<0.05), and the 5-HT and 5-HIAA concentration were significantly decrease in hippocampus in the SZ developmental model group, respectively (P<0.01 or 0.05). CONCLUSION: The activity of 5-HT systems in the mPFC and hippocampus and NE systems in the hippocampus were decreased in SZ developmental model group.

Key words: Schizophrenia, Development, MK-801, NE, 5-HT

中图分类号:

R965.2

唐亚梅, 张向晖, 刘勇. 地佐环平诱导的精神分裂症发育模型大鼠脑组织去甲肾上腺素、5-羟色胺及代谢产物的浓度变化[J]. 中国临床药理学与治疗学, 2012, 17(7): 721-726.

TANG Ya-mei, ZHANG Xiang-hui, LIU Yong. Concentration change of NE, 5-HT and their metabolites in brain tissue in schizophrenia developmental models rat repeatedly treated with MK-801[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(7): 721-726.

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