MCC950调控线粒体丙酮酸载体对阿尔茨海默病模型Tau蛋白影响  

Effect of MCC950 Regulation of Mitochondrial Pyruvate Carrier on Tau Protein in Alzheimer's Disease Model

作　　者：齐越 安阳[2] 董笑博 夏春鹏 王籍贤 范广坤 李纪彤 李昭[4] QI Yue;AN Yang;DONG Xiaobo;XIA Chunpeng;WANG Jixian;FAN Guangkun;LI Jitong;LI Zhao(Xuzhou Higher Vocational School of Medicine,Xuzhou 221116,Jiangsu,China;Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;First Affiliated Hospital of Ningbo University,Ningbo 315010,Zhejiang,China;Shenyang Medical College,Shenyang 110002,Liaoning,China)

机构地区：[1]徐州医药高等职业学校,江苏徐州221116 [2]辽宁中医药大学,辽宁沈阳110847 [3]宁波大学附属第一医院,浙江宁波315010 [4]沈阳医学院,辽宁沈阳110002

出　　处：《中西医结合慢性病杂志》2024年第1期6-12,共7页JOURNAL OF INTEGRATED TRADITIONAL CHINESE AND WESTERN MEDICINE ON CHRONIC DISEASES

基　　金：江苏省药品监管科学科研计划重大项目(202309);浙江省教育厅项目(ZX2021000605);徐州市科技局项目(KC22134)。

摘　　要：目的探讨MCC950通过抑制线粒体丙酮酸载体降低阿尔茨海默病模型Tau蛋白的作用机制。方法采用冈田酸(20 nmol/L)诱导SH-SY5Y细胞,添加UK5099(1μmol/L),CCK8法检测细胞生存率;免疫荧光法测定AT-8表达;荧光探针法测定活性氧;Rho 123测定线粒体膜电位;Western blot测定丙酮酸载体及Tau-5表达水平;ELISA法测定NOD样受体蛋白3、白细胞介素-1β、白细胞介素-18含量。结果MCC950在10μmol/L浓度下对SH-SY5Y细胞具有保护作用(P<0.01);可增加线粒体膜电位,减少活性氧的产生,抑制AT-8、Tau-5、白细胞介素-1β、白细胞介素-18及丙酮酸酶载体的表达(P<0.05或P<0.01),但对NOD样受体蛋白3无明显抑制作用。结论MCC950对冈田酸诱导的SH-SY5Y细胞具有减少炎症因子、抑制Tau蛋白过度磷酸化的作用,其作用机制与抑制丙酮酸载体、改善线粒体功能有关。Objective To investigate the mechanism of MCC950 reducing Tau protein in Alzheimer's disease model by inhibiting mitochondrial pyruvate carrier(MPC).Methods SH-SY5Y cells were induced by gonadic acid(20 nmol/L),supplemented with UK5099(1μmol/L),and the survival rate of SH-SY5Y cells was detected by CCK8 method.The expressions of AT-8 was determined by immunofluorescence method.Active oxygen species was determined by DCFHDA method.Mitochondrial membrane potential was measured by Rho 123.The expression levels of MPC and IL-1βwere determined by Western blot.The levels of NLRP3,IL-1βand IL-18 were determined by ELISA.Results MCC950 had a protective effect on SH-SY5Y cells at 10μmol/L concentration(P<0.01).It could increase the mitochondrial membrane potential,decrease the production of reactive oxygen species,and inhibit the expression of AT-8,Tau-5,IL-18,IL-1βand MPC(P<0.05 or P<0.01),but it had no signicant inhibitory effect on NLRP3.Conclusion MCC950 can reduce the expression of inflammasome and inhibit Tau hyperphosphorylation in okada-induced SH-SY5Y cells.The mechanism is related to inhibiting mitochondrial pyruvate carrier and improving mitochondrial function.

关 键 词：MCC950 阿尔茨海默病 丙酮酸载体 TAU蛋白 线粒体膜电位 活性氧 

分 类 号：R277.7[医药卫生—中医学] R749.16