辛伐他汀通过抑制类异戊二烯的合成降低TDP-25细胞和hSOD1G93A细胞的活力  

Simvastatin decreased cell viability of TDP-25 cells and hSODlG93A cells by inhibiting isoprenoid synthesis

作　　者：齐伟静[1] 刘亚玲[2] 李睿 杨帅[1] 李帅[2] 耿丽颖 张欣[1] 钱倩 Qi Weijing;Liu Yaling;Li Rui;Yang Shuai;Li Shuai;Geng Liying;Zhang Xin;Qian Qian(Department of Neurology,the Baoding No.1 Central Hospital,Hebei 071000,China)

机构地区：[1]保定市第一中心医院神经内科,河北071000 [2]河北医科大学第二医院神经内科,河北省神经病学重点实验室

出　　处：《脑与神经疾病杂志》2021年第3期133-137,共5页Journal of Brain and Nervous Diseases

基　　金：国家自然科学基金(81871001);河北省卫生健康委科研基金项目(20200265)。

摘　　要：目的观察辛伐他汀对肌萎缩侧索硬化(ALS)的两种细胞模型:TDP-25细胞和hSOD1G93A细胞活力的影响.方法辛伐他汀、辛伐他汀联合甲羟戊酸途径的下游产物以及下游抑制剂分别干预TDP-25细胞和hSOD1G93A细胞,应用CCK-8法和LDH法检测细胞活力的变化.结果辛伐他汀降低了TDP25细胞和hSOD1G93A细胞的活力,呈剂量依赖性和时间依赖性.辛伐他汀导致的细胞活力下降可以通过补充甲羟戊酸,FPP或GGPP而完全缓解,但补充胆固醇不能.另外,FTI-277可以明显降低TDP-25细胞的活力,GGTI-286可以同时降低TDP-25细胞和hSOD1G93A细胞的活力,而胆固醇抑制剂AY9944对两种细胞的活力均无明显影响.结论辛伐他汀导致TDP-25细胞和hSOD1G93A细胞的活力下降,这种细胞毒性作用可能是由于抑制了类异戊二烯的合成.Objective To observe the effect of simvastatin on cell viability of amyotrophic lateral sclerosis(ALS)cell models:TDP-25 cells and hSODlG93A cells.Methods Simvastatin combined with mevalonate pathway products,and mevalonate pathway downstream inhibitors were used to incubate TDP-25 cells and hSODlG93A cells.CCK-8 and LDH were used to detect changes in cell viability.Results Simvastatin decreased cell viability of TDP-25 cells and hSODlG93A cells in a dose-and time-dependent manner.The addition of mevalonate,FPP or GGPP could improve the cell damage caused by simvastatin,whereas cholesterol could not reverse the toxic effect of simvastatin.FTI-277 could induce a significant decrease in cell viability of TDP-25 cells,GGTI-286 significantly decreased cell viability of TDP-25 cells and hSODlG93A cells,while AY9944 had no significant effect on cell viability of TDP-25 cells or hSODlG93A cells.Conclusions Simvastatin decreased cell viability of TDP-25 cells and hSODlG93A cells,and these cytotoxic effects were related to the inhibition of isoprenoid synthesis.

关 键 词：辛伐他汀 肌萎缩侧索硬化 类异戊二烯 TDP25细胞 hSOD1G93A细胞 

分 类 号：R744.8[医药卫生—神经病学与精神病学]