中文摘要：

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,NM-DA）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6d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7～10d皮下注射MK-801（0.1mg/kg,bid）,SZ慢性给药模型大鼠于出生后47～60d腹腔注射MK-801（0.2mg/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63d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-hydroxyin-doleacetic 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。

英文摘要：

AIM. To explore the related neu- robiochemistry pathomechanism by the compari- son of concentration of norepinephrine （NE）, 5- hydroxytryptamine （5-HT） and their metabo- lites in brain tissue in the schizophrenia （SZ） de- velopmental model rats. METHODS： 24 neo- natal male Spragur-Dawley （SD） rats were ran- domly assigned at the postnatal day 6 to 3 groups： a SZ developmental model group （sub- cutaneous injection with MK-801 at the postna- tal day 7-10, 0.1 mg/kg bid）, a chronic medica- tion model group （intraperitoneal injection at the postnatal day 47-60, 0. 2 mg/kg, qd） and a nor- mal 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 Electroehemic detection for high performance liquid chromatogram （HPLC） tech- nique. 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 in- creased （P〈0.05）, and the 5-HT and 5-HIAA concentration were significantly decrease in hip- pocampus in the SZ developmental model group, respectively （P 〈 0.01 or 0.05）. CONCLU- SION： The activity of 5-HT systems in the mPFC and hippocampus and NE systems in the hippocampus were decreased in SZ developmen- tal model group.