ERK1/2介导姜黄素抑制STS诱导神经元毒性损伤的作用  

ERK1 /2 mediated inhibitory role of curcumin on STS-induced neurons toxic injury

作　　者：曹畅[1,2] 刘婷婷[1,2] 蔡哲平 张淑萍[1,2] 覃筱燕[1,2] 

机构地区：[1]中央民族大学北京市食品环境与健康工程技术研究中心,北京100081 [2]中央民族大学生命与环境科学学院,北京100081

出　　处：《中国生化药物杂志》2015年第4期1-4,共4页Chinese Journal of Biochemical Pharmaceutics

基　　金：国家自然科学资金(31372225);中央民族大学985工程资助项目(YLDX01013);国家大学生创新训练计划资助项目(GCCX2015110019)

摘　　要：目的观察姜黄素对星形孢菌素(staurosporine,STS)介导的神经元毒性损伤细胞存活率的影响,以阐明细胞外信号调节激酶(extracellular signal-regulated kinase 1/2,ERK1/2)介导姜黄素抑制STS诱导神经元毒性损伤的作用。方法运用SD大鼠乳鼠海马神经元原代培养细胞,STS诱导建立细胞毒性损伤模型。实验随机分6组:正常对照组、STS模型组、PD098059+STS模型组、姜黄素+STS预处理组、姜黄素+PD098059+STS组和姜黄素组。用MTT法测定细胞活性,以乳酸脱氢酶(lactate dehydrogenase,LDH)释放率分析细胞毒性,4',6-二脒基-2-苯基吲哚(DAPI)染色观察细胞凋亡效应,Western blot法检测ERK1/2在姜黄素预处理对STS介导神经元凋亡抑制中的作用。结果姜黄素+STS预处理组的细胞活性比STS模型组明显升高(P<0.001);与PD098059+STS模型组比较,姜黄素+PD098059+STS预处理组细胞活性差异无统计学意义;与姜黄素+STS预处理组比较,姜黄素+PD098059+STS神经元存活率明显降低(P<0.001);姜黄素+STS预处理组的细胞毒性明显小于STS模型组(P<0.001)。STS模型组呈现典型的细胞凋亡特征,姜黄素可抑制STS介导的神经元凋亡;姜黄素+STS预处理组p-ERK1/2蛋白表达量明显高于STS模型组(P<0.001)。结论姜黄素通过上调p-ERK1/2的表达抑制STS介导的神经元毒性损伤;PD098059阻断神经细胞p-ERK1/2的表达后,姜黄素抑制STS介导的神经元毒性损伤作用未能顺利实施,说明ERK1/2能够介导姜黄素抑制STS诱导神经元毒性损伤。Objective To explore extracellular signal-regulated kinase （ ERK1/2 ） expression in the role of curcumin inhibited staurosporine （STS）-mediated neurons toxic injury through added PD098059, and to clarify ERK1/2 mediated inhibitory role of curcumin on STS-induced neurons toxic injury.Methods The neurons toxic injury model of primary cultured hippocampal neurons was established by STS.The experiment was divided into six groups：normal control group, STS model group, PD098059 ＋STS model group, curcumin ＋STS pretreatment group, curcumin＋PD098059＋STS treatment group and curcumin treatment group.The cell viability were determined by MTT method, lactate dehydrogenase （LDH） release rate, cell toxicity were detected, nuclear shape were observed by DAPI staining, and ERK1/2 expression were detected by Western blot method.Results The cell viability of curcumin ＋STS pretreatment group was significantly higher than STS model group （ P 〈0.001 ）; the cell viability had no significant difference between PD098059 ＋STS model group and curcumin ＋PD098059 ＋STS treatment group;compared with curcumin ＋STS model group , the cell viability of curcumin ＋PD098059 ＋STS treatment group was significantly decreased （ P〈0.001 ）.LDH results showed that the nerve cell toxicity of curcumin ＋STS pretreatment group was obviously less than STS model group （P〈0.001）.The cell nuclear shape showed typical apoptosis morphological characteristics in STS model group, and curcumin inhibited the effect of STS mediated-neuronal apoptosis.ERK1/2 protein expression in curcumin ＋STS pretreatment group significantly increased compared with STS model group （ P 〈0.001 ） .Conclusion Curcumin inhibited STS-mediated neurons toxicity injury by up-regulating ERK1/2 expression.After PD098059 blocking the nerve cells ERK1/2 synthesis, the inhibitory action of curcumin failed to implemented, which illustrated that ERK1/2 mediated curcumin to inhibit STS-induced neuronal toxic injury.

关 键 词：ERK1/2 姜黄素 星形孢菌素 海马神经元 PD098059 

分 类 号：R285.5[医药卫生—中药学]