丁基苯酞对大脑中动脉阻断后皮层组织中花生四烯酸释放及磷脂酶A2基因表达的影响

目的　研究丁基苯酞（dl-NBP), d-NBP和 l-NBP对大脑中动脉阻断(MCAO) 6 h后缺血区皮层中花生四烯酸(AA)释放及磷脂酶A₂（PLA₂）基因表达的影响。方法　阻断大脑中动脉起始部造成局灶性脑缺血模型。HPLC检测AA。Northern blot检测皮层中PLA₂基因表达。结果　MCAO后6 h，皮层中AA释放明显增加。于脑缺血后5 min 和120 min，给dl-NBP(10或20 mg.kg^-1) 和尼莫地平(0.5 mg.kg^-1) 可显著抑制AA的释放。d-NBP和l-NBP作用比较，显示d-NBP有与dl-NBP相似的作用，而l-NBP则无明显影响。Northern印迹结果表明，脑缺血6 h，皮层中PLA₂的基因表达增强。 dl-NBP和d-NBP(10, 20 mg.kg^-1,ip)皆可使表达降低，而l-NBP对缺血脑组织中PLA₂的基因表达的升高无明显影响。结论　dl-NBP和d-NBP可抑制MCAO后脑组织中AA释放和PLA₂的基因表达。

EFFECTS OF DL-3-n-BUTYLPHTHALIDE ON ARACHIDONIC ACID RELEASE AND PHOSPHOLIPASE A2 mRNA EXPRESSION IN CEREBRAL CORTEX AFTER MIDDLE CEREBRAL ARTERY OCCLUSION IN RATS

AIM　To study the effect of dl-3-n-butylphthalide (dl-NBP) on arachidonic acid(AA) release and phospholipase A₂ (PLA₂) mRNA in cerebral cortex of rats subjected to focal cerebral ischemia. METHODS　Focal cerebral ischemia was induced by inserting a monofilament nylon suture into the internal carotid artery and blocking the origin of the middle cerebral artery. AA was determined with high performance liquid chromatography (HPLC). The PLA₂ mRNA expression was evaluated by Northern blot analysis. RESULTS　Six hours of cerebral ischemia induced AA release in the ischemic cerebral cortex. dl-NBP (10 or 20 mgkg^-1) and nimodipine (0.5 mg.kg^-1) given intraperitoneally 5 min and 120 min again after the onset of ischemia significantly reduced AA concentration in the cerebral cortex (P<0.01). d-NBP, but not l-NBP, decreased AA release in the brain after middle cerebral artery occlusion. The expression of PLA2 mRNA in cerebral cortex induced by cerebral ischemia was also inhibited by dl-NBP and d-NBP (10 or 20 mg*kg^-1, ip). CONCLUSION　dl-NBP and d-NBP inhibited AA release and PLA₂ mRNA expression in the ischemic brain tissue in vivo.