Aβ_(25～35)通过激活p38MAPK信号通路促进大鼠心肌细胞凋亡  

Aβ_(25-35) induce the apoptosis of rat cardiomyocytes via p38MAPK pathway

作　　者：卢永浩[1] 吴昊[1] 张恒谦[1] 

机构地区：[1]沈阳医学院附属中心医院神经外科,沈阳110024

出　　处：《重庆医学》2015年第34期4771-4773,4776,共4页Chongqing medicine

基　　金：辽宁省教育厅科研基金资助项目(L2014413)

摘　　要：目的 观察β淀粉样蛋白25-35（Aβ25-35）对培养大鼠心肌细胞的毒性作用,并阐明可能的机制。方法 体外培养大鼠心肌细胞,给予不同浓度Aβ25-35激,采用流式细胞术检查细胞凋亡率,采用Western blot方法测定凋亡相关蛋白Bax和Bcl-2的表达水平。观察Aβ25-35对p38丝裂原活化蛋白激酶（MAPK）磷酸化的影响,并进一步评估p38MAPK特异性抑制剂对Aβ25-35导心肌细胞凋亡的影响。结果 Aβ25-35可以诱导体外培养大鼠心肌细胞凋亡,升高促凋亡蛋白Bax的表达,下调抗凋亡蛋白Bcl-2的表达,且呈现浓度依赖的关系。同时发现给予Aβ25-35p38MAPK磷酸化水平增加,而给予p38MAPK特异性抑制剂SB203580减少心肌细胞的凋亡。结论 Aβ25-35以导致体外培养的大鼠心肌细胞发生凋亡,而p38MAPK信号通路可能参与了该过程。本研究探索阿尔兹海默病（AD）患者心肌损伤的可能发病机制,为将来有效防治AD相关性心肌损伤提供新思路。Objective To observe the cytotoxicity of β25-35 in cultured rat cardiomocytes, and to elucidate the possible mechanism. Methods The isolated rat myocardial cells were cultured in vitro. Following the stimulation of β25-35 with different dose,the apoptosis of cardiomyocytes were observed by flow cytometry. Bax and Bcl-2 were simultaneously measured by Western blot. The phosphorylated p38 mitogen activated protein kinase（p38MAPK） were evaluated by Western blot under the stimulation of 20μmol/L Aβ25-35. At the same time,the effect of p38MAPK selective inhibitor SB203580 on the apoptosis of cardiomycytes in- duced by 20μmol/L β25-35 also was evaluated. Results β25-35 induced the apoptosis of rat myocardial cells. Meanwhile, the expression of Bax increased and the expression of Bcl-2 decreased in dose-dependent mode. The level of phosphorylated p38MAPK in myocardial cells exposed to 20μmol/L β25-35 increased obviously. However, the apoptosis was inhibited by p38MAPK selective in-hibitor SB203580. Conclusion β25-35 could induce the apoptosis of rat cardiomyocytes via p38MAPK pathway. The study will help identify the possible mechanisms of cardiomocytes injury in Alzheimer＇s disease（AD） and provide a new strategy for clinical treatment of AD-associated myocardial injury.

关 键 词：P38丝裂原活化蛋白激酶类 阿尔兹海默病 细胞凋亡 

分 类 号：R542.2[医药卫生—心血管疾病]