白藜芦醇通过ROS-JNK通路抑制晚期糖基化终末产物诱导PC12细胞凋亡  

Resveratrol inhibits advanced glycation end products induced PC12 cell apoptosis through ROS-JNK pathway

作　　者：姜磊 路延超[4] 张家恺 张睿 许顺江[3] 张国军[1,2,6] JIANG Lei;LU Yan-chao;ZHANG Jia-kai;ZHANG Rui;XU Shun-jiang;ZHANG Guo-jun(Laboratory Diagnosis Center,Beijing Tiantan Hospital Affiliated to Capital Medical University;Beijing Engineering Research Center of Immunological Reagents Clinical Research,Beijing 100070,China;Central Laboratory,the First Hospital of Hebei Medical University,Shijiazhuang 050031,China;Dept of Nuclear Medicine,the First Hospital of Hebei Medical University,Shijiazhuang 050031,China;Dept of Radiology,the First Hospital of Hebei Medical University,Shijiazhuang 050031,China;NMPA Key Laboratory for Quality Control of In Vitro Diagnostics,Beijing 100070,China)

机构地区：[1]首都医科大学附属北京天坛医院实验诊断中心 [2]北京市免疫试剂临床工程技术研究中心,北京100070 [3]河北医科大学第一医院中心实验室,河北石家庄050031 [4]河北医科大学第一医院核医学科,河北石家庄050031 [5]河北医科大学第一医院放射科,河北石家庄050031 [6]国家药监局体外诊断试剂质量控制重点实验室,北京100070

出　　处：《中国药理学通报》2021年第8期1104-1109,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No 81570728);中央引导地方科技发展资金项目(No 206Z7701G);河北省引进国外智力项目(No 2019YX007A);河北省卫生健康委员会基金项目(No 20180209)。

摘　　要：目的探讨白藜芦醇(resveratrol,RSV)对晚期糖基化终末产物(AGEs)诱导大鼠嗜铬细胞瘤(PC12)细胞损伤的保护作用及可能的分子机制。方法MTS检测不同浓度AGEs(0、50、100、200、400 g·L^(-1))和不同浓度RSV(0、5、10、20、40μmol·L^(-1))对细胞存活率的影响。AGEs(400 g·L^(-1))和RSV(10μmol·L-1)联合处理PC12细胞,TUNEL染色检测细胞凋亡;流式细胞术检测细胞凋亡和活性氧(ROS)水平;Western blot检测相关蛋白(p-JNK、JNK、PUMA、Bcl-2、Bax和Caspase-3)的表达。JNK特异性磷酸化抑制剂(SP600125)预处理,流式细胞术观察细胞凋亡。结果与正常组比较,AGEs组细胞存活率降低,细胞凋亡率和ROS水平增加,p-JNK、PUMA、Bax和caspase-3表达增加,Bcl-2表达降低;与AGEs组比较,AGEs+RSV组细胞存活率升高,细胞凋亡率和ROS水平降低,p-JNK、PUMA、Bax和caspase-3表达降低,Bcl-2表达增加。SP600125可部分逆转AGEs对PC12细胞凋亡的作用。结论RSV可显著抑制AGEs诱导的PC12细胞凋亡,其机制可能与激活ROS-JNK通路有关。Aim To investigate the effect of resveratrol(RSV)on apoptosis of PC12 cells induced by advanced glycation end products(AGEs)and its possible molecular mechanism.Methods MTS assay was used to detect the effects of AGEs(0,50,100,200,400 g·L^(-1))and RSV(0,5,10,20,40μmol·L^(-1))on cell viability.PC12 cells were treated with AGEs(400 g·L^(-1))and RSV(10μmol·L^(-1)).TUNEL staining was used to detect apoptosis;flow cytometry was used to detect apoptosis and reactive oxygen species(ROS);Western blot was used to detect protein expression of p-JNK,JNK,PUMA,Bcl-2,Bax and Caspase-3.Apoptosis was observed by flow cytometry after pretreatment with JNK specific phosphorylation inhibitor(sp600125).Results Compared with normal control group,the cell viability of AGEs group decreased,the apoptotic rate and ROS levels increased,the expressions of p-JNK,PUMA,Bax and Caspase-3 protein increased,the expression of Bcl-2 protein decreased;Compared with AGEs group,the cell viability of the AGEs+RSV group increased,the levels of apoptotic rate and ROS were reduced,the expressions of p-JNK,PUMA,Bax and caspase-3 protein decreased,the expression of Bcl-2 protein increased.Sp600125 could partially reverse the effect of AGEs on PC 12 cell apoptosis.Conclusions RSV can significantly inhibit the apoptosis of PC 12 cells induced by AGEs,which may be related to the activation of ROS-JNK pathway.

关 键 词：白藜芦醇 晚期糖基化终末产物 PC12细胞 凋亡 ROS-JNK通路 JNK特异性磷酸化抑制剂(SP600125) 

分 类 号：R284.1[医药卫生—中药学] R285.5[医药卫生—中医学]