氟哌啶醇对大鼠离体海马脑片和原代神经元缺糖/缺氧和N-甲基-D-天冬氨酸损伤的保护作用  

PROTECTIVE EFFECT OF HALOPERIDOL ON OXYGEN/GLUCOSE DEPRIVATION-AND NMDA-INDUCED INJURIES ON RAT HIPPOCAMPAL SLICES AND PRIMARY NEURONS

作　　者：严乐勤[1] 魏尔清[1] 沈建中[1] 沈波[1] 

机构地区：[1]浙江大学医学院神经生物学实验室,药理学实验室,浙江杭州310031

出　　处：《药学学报》2002年第12期922-926,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 ( 39770 2 70 ) ;浙江省自然科学基金资助项目 ( 3990 90 )

摘　　要：目的　观察氟哌啶醇对大鼠离体海马脑片和原代神经元的缺糖 缺氧 (OGD)和N 甲基 D 天冬氨酸 (N methyl D aspartate ,NMDA)损伤的潜在保护作用及其机制。方法　海马脑片OGD以无葡萄糖的人工脑脊液中通 95 %N2 +5 %CO2 诱导。通过测定TTC染色后形成的红色产物来分析脑片活性。结果　氟哌啶醇 (1和 10 μmol·L- 1 )抑制OGD损伤 ,抑制率分别为 17 7%和 2 5 %,而D2 多巴胺受体拮抗剂多潘立酮无此作用。NMDA也能显著降低海马脑片及原代神经元的活性 ,而氟哌啶醇可抑制这一损伤作用。结论　氟哌啶醇对大鼠离体海马脑片OGD和原代神经元NMDA损伤有保护作用。AIM To investigate the potential neuroprotective effect of haloperidol on oxygen/glucose deprivation (OGD)- and N-methyl-D-aspartate (NMDA)-induced injuries on rat hippocampal slices in vitro and hippocampal neurons in primary culture, and the possible mechanism. METHODS OGD was performed in glucose-free artificial cerebrospinal fluid bubbled with 95% N 2 + 5% CO 2 in rat hippocampal slices. The viability of the slices was determined by measuring TTC formazan product. Hippocampal slices and primary neurons were also used to determine the toxic effect of NMDA and the protective effect of haloperidol. RESULTS OGD for 1 h significantly decreased the TTC staining of hippocampal slices. Haloperidol at 1 and 10 μmol·L -1 significantly inhibited OGD-induced decrease by 17.7% and 25% respectively, but domperidone, a D 2 dopamine receptor antagonist, did not show this effect. Dopamine did not affect the viability of normal hippocampal slices. Like OGD insult, NMDA challenge significantly decreased both the viabilities of hippocampal slices and cultured primary neurons, which were prevented by haloperidol co-treatment. CONCLUSION Haloperidol exhibited protective effect on OGD-induced injury of rat hippocampal slices and NMDA-induced injuries on both hippocampal slices and primary neurons. Its effect on OGD insult may be via mechanisms beyond dopamine-receptor blockade, but probably related to NMDA-receptor inhibition.

关 键 词：氟哌啶醇 海马 原代神经元 N-甲基-D-天冬氨酸 药理学 脑片缺糖缺氧性损伤 

分 类 号：R965[医药卫生—药理学] R971.4[医药卫生—药学]