八肽胆囊收缩素对谷氨酸诱导神经元死亡的拮抗作用及机制研究

PROTECTIVE EFFECTS OF CCK-8 ON GLUTAMATE-INDUCED NEURONAL CELL DEATH IN NEURONAL CELL CULTURES

以谷氨酸、ＮＭＤＡ作用原代培养的大鼠大脑皮层神经元，随药物浓度递增，作用时间延长，细胞存活率逐渐下降。八肽胆囊收缩素对谷氨酸、ＮＭＤＡ诱导的神经元死亡具有明显的拮抗作用，在其浓度为１×１０－７ｍｏｌ／Ｌ时其拮抗率为７７８±４４％和７５４±６７％。ＣＣＫＢ受体拮抗剂Ｌ－３６５２６０可完全阻断八肽胆囊收缩素的保护作用，而ＣＣＫＡ受体拮抗剂Ｌ－３６４７１８无此作用。应用Ｆｕｒａ－２荧光技术测定新生大鼠大脑皮层神经元细胞内游离钙浓度（［Ｃａ２＋］ｉ），八肽胆囊收缩素可明显抑制ＮＭＤＡ诱导的神经元［Ｃａ２＋］ｉ升高，在浓度为１×１０－７ｍｏｌ／Ｌ时其抑制率为９５７％。结果显示：八肽胆囊收缩素可能通过其Ｂ受体产生拮抗谷氨酸神经兴奋毒性作用，抑制Ｃａ２＋内流是其产生拮抗作用的机制之一。

The protective effects of cholecystokinin-octapetide (CCK-8) on glutamate-induced cytotoxicity were examined using cultured rat's cortical neurons. Cell viability was significantly reduced when the cultures were expoxed to glutamate (0 5×10 -8 mol/L) or N-mthely-D-aspartate (NMDM) for 30 min. Glutamate-induced neurotoxicity can be significantly inhibited by CCK-8 at concentration of 10 -9 ～10 -6 mol/L. The neuroprotective effects CCK can be inhibited by CCK B receptor antagonist L-365260,but not by CCK A receptor antagonist L-364718. NMDA-induced Ca 2+ influx was measured. The Ca 2+ influx also can be inhibited by CCK. These results indicated:CCK-8 may prevent glutamate neurotoxicity via. CCK B recepetor and this protective mechanism may be due to inhibiting Ca 2+ influx.