桃红四物汤颗粒通过改善线粒体功能障碍和氨基酸代谢紊乱缓解鱼藤酮诱导的SH-SY5Y细胞毒性作用  

Taohong Siwu dispensing granules alleviate rotenone-induced SH-SY5Y cellular cytotoxicity by rescuing mitochondrial dysfunction and amino acid metabolism disarrangements

作　　者：李双 董明纲[2] 郭春燕[1,3] 李双双 尤斯涵 万叶 刘心星 Shuang Li;Minggang Dong;Chunyan Guo;Shuangshuang Li;Sihan You;Ye Wan;Xinxing Liu(Department of Pharmacy,Hebei North University,Zhangjiakou 075000,Hebei,China;School of Laboratory Medicine,Hebei North University,Zhangjiakou 075000,Hebei,China;Hebei Key Laboratory of Neuropharmacology,Zhangjiakou 075000,Hebei,China;Zhangjiakou Jianyuan Technology Co.,Ltd.,Zhangjiakou 075000,Hebei,China)

机构地区：[1]河北北方学院药学系,河北张家口075000 [2]河北北方学院医学检验学院,河北张家口075000 [3]河北省神经药理学重点实验室,河北张家口075000 [4]张家口健垣科技有限公司,河北张家口075000

出　　处：《Journal of Chinese Pharmaceutical Sciences》2023年第5期360-378,共19页中国药学（英文版）

基　　金：The Natural Science Foundation of Hebei Province(Grant No.H2021405021);the Hebei Provincial Administration of Traditional Chinese Medicine(Grant No.2017102);the Hebei Education Department(Grant No.ZD2019107)。

摘　　要：帕金森氏病(PD)是一种进行性神经系统疾病,以震颤和运动缓慢为特征。线粒体功能障碍和氨基酸代谢是PD疾病的重要机制。前期工作证实SH-SY5Y细胞中氨基酸含量的变化早于细胞活力的变化。本研究旨在探讨桃红四物配方颗粒(THSWDG)是否能够减轻鱼藤酮诱导的SH-SY5Y细胞毒性,是否能够改善鱼藤酮诱导线粒体功能障碍及氨基酸代谢紊乱。用MTT法分析细胞存活率;JC-1染色法测定线粒体膜电位;高效液相色谱法测定SH-SY5Y细胞中氨基酸的含量。采用主成分分析法分析氨基酸含量的变化趋势;使用生物信息学工具进一步阐明其潜在机制。研究表明,SH-SY5Y细胞氨基酸含量的变化早于细胞活性的变化。THSWDG能显著提高细胞存活率,改善鱼藤酮对线粒体膜电位的影响和氨基酸的异常代谢。生物信息分析结果表明,THSWDG的作用涉及9个生物学过程,包括5个与PD疾病相关的氨基酸代谢调节过程和4个与氧化损伤相关的生物学过程。细胞氨基酸过程是一种常见的调节氨基酸代谢和氧化损伤的生物过程。提示THSWDG通过改善线粒体功能障碍和氨基酸代谢紊乱对鱼藤酮诱导的SH-SY5Y细胞损伤发挥保护作用。As a progressive neurological disorder,Parkinson’s disease(PD)is characterized by tremors and slow movement.Mitochondrial dysfunction and amino acid(AA)metabolism are essential mechanisms of PD.Previous work has confirmed that the changes in amino acid contents in SH-SY5Y cells are earlier than the changes in cell viability.In the present study,we aimed to investigate whether Taohong Siwu dispensing granules(THSWDG)could alleviate rotenone-induced SH-SY5Y cytotoxicity by improving mitochondrial dysfunction and amino acid metabolism disorder.MTT assay was used to analyze the cell viability.JC-1 dye assay was used to measure mitochondrial membrane potential(MMP).HPLC was used to determine the content of amino acids(AAs)in SH-SY5Y cells.Principal component analysis was used to analyze the changes in the content of AAs.In order to further explore the PD-related biological functions involved in amino acid regulation,bioinformatics analysis tools were used to assess the biological processes involved in these protective effects.This study showed that the changes in AA contents in SH-SY5Y cells were earlier than the changes in cell activity.THSWDG dramatically increased cell viability and improved the rotenone-induced repression of MMP and abnormal metabolism of AAs.The results of the bioinformatic analysis suggested that the effects of THSWDG involved nine biological processes,including five AA metabolism regulations related to PD and four biological processes related to oxidative damage.The cellular AA process is a common biological process involved in the regulation of AA metabolism and oxidative damage.These results suggested that THSWDG exerted a cytoprotective effect on SH-SY5Y cells by rescuing mitochondrial dysfunction and AA metabolism disarrangements.

关 键 词：帕金森病 桃红四物汤 氨基酸 鱼藤酮 线粒体膜电位 

分 类 号：R961.1[医药卫生—药理学]