脑活素激发细胞内钙升高介导大脑皮质神经元死亡  

Cerebrolysin Induces Cultured Rat Cortical Neuronal Death by Increasing Intracellular Calcium

作　　者：欧阳颖[1] 林穗珍[1] 李晓瑜[1] 颜光美[2] 杜敏联[1] 

机构地区：[1]中山大学附属第一医院儿科 [2]中山大学中山医学院药理学教研室,广东广州510080

出　　处：《中山大学学报（医学科学版）》2003年第6期528-531,共4页Journal of Sun Yat-Sen University:Medical Sciences

基　　金：国家自然科学基金资助项目(39770782);广东省自然科学基金资助项目(970052)

摘　　要：【目的】探讨脑活素对原代培养大鼠大脑皮质神经元的作用及机制。【方法】采用原代培养的胎鼠大脑皮质神经元,观察脑活素对大脑皮质细胞形态学及生存的影响。用FDA/PI染色法测定细胞生存率,并用Flu-o3/AM与带有自动加样装置的荧光成像96孔板测量仪测定细胞内钙浓度(犤Ca2+犦i)的变化【结果】脑活素为0、0.1、1.0、2.5、5.0、10mL/L时,其存活率分别为100%、43%±3%、38%±5%、32%±3%、22%±2%、19%±1%。地佐环平(MK-801)预处理后,其存活率分别为91%±4%、76%±5%、75%±3%、58%±5%、54%±3%、50%±4%,可保护脑活素的神经毒性。同时脑活素浓度依赖性地触发细胞内钙浓度升高,而MK-801可降低脑活素导致的细胞内钙浓度的升高。【结论】脑活素对原代培养的大鼠大脑皮质神经元具有毒性作用,其机制是通过升高细胞内钙介导的。To investigate the effect of cerebrolysin on primary cultured rat cortical neurons and its mechanisms of action. Primary cultured rat cortical neurons were exposed to cerebrolysin and the survival of cells were observed . The neuronal survival was detected by fluorescein diacetate/propidium iodide(PI) staining. The intracellular i was measured by using the fluorometric light imaging plate reader (FLIPR)with calcium indicator Fluo3/AM. Cerebrolysin induced the death of cortical neurons in a dose dependent manner. At the concentration of 0, 0.1, 1.0, 2.5, 5.0 and 10 mL/L,the survival percentages were 100%, 43%±3%, 38%±5%, 32%±3%, 22%±2%and 19%±1%, respectively. Pretreatment with MK 801, a non competitive excitatory amino acid receptor antagonist, the survival percentages were 91%±4%, 76%±5%, 75%±3%, 58%±5%, 54%±3%and 50%±4%,respectively. Cerebrolysin elevated i in a concentration dependent pattern. MK 801 significantly attenuated the rise of i induced by cerebrolysin. [Conclusion]The neurotoxicity of cerebrolysin on primary cultured rat cortical neurons is mediated by elevating the intracellular i.

关 键 词：脑活素 细胞内钙 大脑皮质 神经元 作用机制 

分 类 号：R994.1[医药卫生—毒理学] R971[医药卫生—药学]