洛伐他汀对谷氨酸诱导的兴奋性毒性损害的神经保护作用  

Neuroprotective effects of lovastatin on glutamate induced excitotoxicity in rat cortical neurons

作　　者：马涛[1] 陈耀民[1] 赵永波[1] 

机构地区：[1]上海交通大学附属第一人民医院神经科,上海200080

出　　处：《实用临床医药杂志》2008年第5期28-32,共5页Journal of Clinical Medicine in Practice

基　　金：美国阿尔茨海默氏症协会基金资助项目(IIRG-06-26070)

摘　　要：目的探讨洛伐他汀(LOV)对谷氨酸诱导的大鼠皮质神经元兴奋性毒性损害的神经保护作用。方法选用孕期17d的SD大鼠。取皮质神经元接种培养。实验分为对照组、谷氨酸组、LOV预处理+谷氨酸组、喜树碱组、LOV预处理+喜树碱组。通过台盼蓝排除实验评估细胞活力及免疫荧光细胞化学技术测定神经元形态。结果与未处理组相比.谷氨酸处理组大部分细胞失去活力(P<0.001),在谷氨酸处理神经元之前,洛伐他汀500 nmol/L预处理3 d、5 d.能显著改善细胞活力(P<0.001)。与未处理组相比,喜树碱处理组大部分细胞失去活力(P<0.001).而在喜树碱处理前应用洛伐他汀预处理1 d、3 d、5 d。未见细胞活力改善(P>0.05)。免疫荧光细胞化学技术测定显示,与未处理组相比,谷氨酸处理组MAP-2阳性神经元显著减少(P<0.001),突起的数目和长度均明显减少.洛伐他汀500nmol/L预处理能减轻谷氨酸诱导的MAP-2阳性神经元形态损害。结论洛伐他汀选择性地减轻谷氨酸诱导的大鼠皮质神经元兴奋性毒性损害及形态损害,提示洛伐他汀对兴奋性毒性损害相关神经病理有潜在的神经保护作用。Objective To observe the effect of lovastatin on glutamate induced excitotoxicity in rat cortical neurons. Methods Cortical neurons were prepared from E17 rat. Cell viability was evaluated with trypan blue dye exclusion test and the morphology and number of neurons was assessed with MAP-2 immunofluorescence staining. Results Trypan blue staining demonstrated that lovastatin pre-treatment 3 d, 5 d, but not 1 d, significantly protected neurons from glutamate induced excitotoxicity. However, lovastatin did not protect neurons against the apoptosis events induced by camptothecin. Immunofluorescence staining demonstrated the number of MAP-2 positive neurons decreased and survival neurons showed a loss of MAP-2 positive dendrites Mter glutamate treatment, which were not visible after lovastatin pre-treatment. Conclusions Lovastatin significantly and selectively attenuated glutamate induced excitotoxicity, indicating that lovastatin has potential neuroprotective effects on excitotoxicity-related neuropathology.

关 键 词：洛伐他汀 谷氨酸 喜树碱 神经保护 大鼠 

分 类 号：R734.34[医药卫生—肿瘤]