红景天苷通过PINK1-Parkin通路在MPP^+诱导的SH-SY5Y细胞中维持线粒体形态和功能  

Salidroside Maintains Mitochondrial Morphology and Function in MPP+induced SH-SY5Y Cells through PINK1-Parkin Pathway

作　　者：张伟[1] 李涛[1] 陈磊[2] 吴雷涛 赵俊杰[1] 高建苑[3] 陈建宗[1] 

机构地区：[1]第四军医大学西京医院中医药研究中心,陕西西安710032 [2]第四军医大学唐都医院神经外科,陕西西安710032 [3]第四军医大学西京医院老年病科,陕西西安710032

出　　处：《现代生物医学进展》2016年第9期1649-1653,共5页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81173590)

摘　　要：目的:研究红景天苷(Salidroside,Sal)对在MPP+诱导SH-SY5Y细胞线粒体形态和功能的影响及其机制。方法:采用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴盐(3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide,MTT)检测细胞活性,Mito Tracker Red CMXRos进行线粒体染色,四甲基罗丹明乙酯(Tetramethylrhodamine ethyl ester,TMRE)检测线粒体膜电位,Western blot检测PINK1和Parkin蛋白表达水平。结果:单纯Sal处理24 h对细胞活性、线粒体形态和MMP无影响(P>0.05)。MPP+(500μM)处理SH-SY5Y细胞24 h后,与正常组比较,细胞活性、MMP水平均降低,线粒体长度减短(P<0.01),并发生碎片化。Sal(25μM)预处理24 h可以显著抑制MPP+诱导的细胞活性降低(P<0.01),并维持线粒体长度和增加MMP水平(P<0.01)。而且,Sal(25μM)预处理24 h可以显著恢复MPP+诱导的PINK1和Parkin蛋白表达水平下降(P<0.01)。结论:体外实验证实Sal可以保护MPP+诱导的SH-SY5Y细胞活性降低、线粒体形态和功能异常,而PINK1-Parkin通路可能是其机制之一,为进一步临床开发Sal治疗PD的新药提供实验依据。Objective： This study aims to investigate the mechanism of Salidroside（Sal） protecting mitochondrial morphology and function in MPP＋induced SH-SY5 Y cells. Methods： 3-（4,5-dimethyl-2-thiazolyl）-2,5-diphenyl-2-H-tetrazolium bromide（MTT） assay was used to test the cell activity; Mito Tracker Red CMXRos was used to test the mitochondrial morphology; Tetramethylrhodamine ethyl ester（TMRE） was used to test the mitochondrial membrane potential（MMP） and Western blot method was used to detect the protein level of PINK1 and Parkin. Results： Sal treatment of 24 h had no effect on cell activity, mitochondrial morphology and MMP（P〈0.05）. When compared with the control group, the cell activity and MMP levels were statistically decreased respectively（P〈0.01）, and the length of mitochondrial was statistically shortened（P〈0.01） and in fragmentation after MPP＋（500 μM） treated 24 h in SH-SY5 Y cells. However,pretreatment with Sal（25 μM） 24 h could significantly inhibit MPP＋induced the decrease of cellular activity（P〈0.01）, and maintain mitochondrial length and increase the level of MMP（P〈0.01）. Moreover, pretreatment with Sal（25 μM） 24 h could significantly inhibit the MPP＋（500 μM） induced the decrease of protein level of PINK1 and Parkin（P〈0.01）. Conclusion： Our vitro experiments showed that Sal could protect the MPP＋induced the decrease of SH-SY5 Y cell activity and shortened the length of mitochondrial and in fragmentation.PINK1-Parkin pathway might be one of the mechanisms. It was provided experimental basis for Sal as a new drug for the treatment of PD.

关 键 词：红景天苷 PINK1 PARKIN 线粒体形态 线粒体膜电位 

分 类 号：R285.5[医药卫生—中药学] R971[医药卫生—中医学]