Genistein通过影响Ca^(2+)/CaM/Cav1.2/CaMKⅡ信号通路抑制Aβ_(25-35)诱导的海马神经元损伤  

Genistein inhibits Aβ_(25-35)-induced hippocampal neurons injury through Ca^(2+)/CaM/Cav1.2 /CaMKⅡ pathway

作　　者：徐毅[1] 林静涵[1] 盛莉[1] 崔政[1] 张黎明[1] 

机构地区：[1]哈尔滨医科大学附属第一医院神经内科,黑龙江哈尔滨150001

出　　处：《中风与神经疾病杂志》2015年第7期586-589,共4页Journal of Apoplexy and Nervous Diseases

摘　　要：目的探讨植物雌激素染料木素(Genistein,GST)对Aβ25-35引起海马神经元钙超载损伤的抑制作用及其机制。方法本实验分为以下4组:正常对照组,Aβ25-35组,Aβ25-35+Genistein组(Aβ25-35+GST组),Aβ25-35+17β-雌二醇组(Aβ25-35+E2组),通过MTT比色法测定细胞活性,选取Genistein的最适浓度。采用Aβ25-35处理建立海马神经元损伤模型。利用Tuj1染色观察神经元生长状态,激光共聚焦扫描观察Genistein对[Ca2+]i的影响,通过Western blot技术检测Ca M、Cav1.2、p-Ca MKⅡ/Ca MKⅡ蛋白表达的变化。结果 0.3μg/ml Genistein能明显抑制Aβ25-35引起细胞活性降低及[Ca2+]i增加,并能对抗Aβ25-35引起的Ca M,Cav1.2蛋白水平增加及p-Ca MKⅡ减少。结论 Genistein具有拮抗Aβ25-35所致海马神经元钙超载损伤的作用,其作用机制可能与Ca2+/Ca M/Cav1.2/Ca MKⅡ信号通路有关,为Genistein进一步应用于临床治疗神经退变性疾病提供理论依据。Objective To investigate the effect and potential molecular mechanisms of Genistein on Aβ25-35-induced hippocampal neurons injury. Methods A1325-35 was used for establishing the damage model of hippocampal neurons. The cells were treated with Aβ25-35s alone,Aβ25-35 and Genistein,Aβ25-35 and E2 or solvent（Ctl）. Cell viability was detected by MTF assay,the injury model was established by Aβ25-35 treatment, cellular morphology was observed by Tujl immunofluo- rescence staining, [ Ca^2＋ ] i level was evaluated by confocal technique, the protein level of CaM, p-CaMK Ⅱ /CaMK Ⅱ , Cavl. 2 were detected by Western blot. Results Genistein 0.3 μg/ml decreased the cell viability and increased the intra- cellular Ca^2＋. Genisten inhibited the upregulation of CaM ,p-CaMK Ⅱ /CaMK Ⅱ ,Cavl. 2 level induced by Aβ25-35. Con- clusion Genistein has the ability of neuron protection through affecting Ca^2＋/CaM/Cavl. 2/CaMK Ⅱ pathway, and the present data provide new insight into the clinical function of Genistein.

关 键 词：GENISTEIN 阿尔茨海默病 钙超载 钙调蛋白 Cav1.2 钙/钙调素依赖性蛋白激酶Ⅱ 

分 类 号：R749.16[医药卫生—神经病学与精神病学]