赛庚啶对谷氨酸诱导的神经元损伤的影响及可能机制

Protective Effects and Mechanism of Cyproheptadine on Neuronal Injury Induced by Glutamate in Rat Primary Cortical Cultures

目的 :观察赛庚啶 (Cyproheptadine,CPH)对谷氨酸 (Glutamate ,Glu)诱导的大鼠大脑皮质神经细胞兴奋毒性的影响及其可能机制。方法 :实验分 5组 ,①对照组 ;②Glu组 ;③Glu +1μmol·L-1CPH组 ;④Glu +10 μmol·L-1CPH组 ;⑤Glu +10 0 μmol·L-1CPH组 ,用倒置显微镜观察神经细胞形态的变化 ,用Trypanblue染色法观察细胞死亡率 ,测定乳酸脱氢酶 (LDH)和总过氧化物歧化酶 (T SOD)的变化。结果 :5 0 μmol·L-1Glu使细胞死亡率升高 ,LDH释放显著增加 ,T SOD降低。 10 ;10 0 μmol·L-1CPH能减少LDH的释放 ,降低细胞死亡率 ,1;10 ;10 0 μmol·L-1CPH还能升高T SOD。结论 :CPH对Glu介导的神经元损伤有保护作用 ,其机制可能与提高T SOD的活性 ,使神经细胞抵抗自由基攻击的能力和抗脂质过氧化作用增强有关。

Objective:To investigate the neuroprotective effect and mechanism of Cyproheptadine(CPH) on glutamate induced neurotoxicity in rat primary cortical cultures. Methods:The effects of glutamate(Glu) and CPH on neurons morphology were observed by discrepancy microscope. Trypan blue method determined the neuron mortality. The release of Lactate dehydrogenase(LDH) and the content of T SOD were measured in neurons. Results:50 μmol·L -1 Glu obviously increased the mortality and the release of LDH,reduced the activity of T SOD. 10?100 μmol·L -1 CPH could decreased the mortality and the release of LDH,1?10?100 μmol·L -1 elevated the activity of T SOD. Conclusion:CPH has an protective effect on Glu induced neurotoxicity in primary cortical cultures. Its mechanism is related to the increasing of T SOD in neurons,which suggesting the capability of anti lipid peroxide reaction and deleting free radicals enhanced.