摘要
目的:探讨硒对病毒性心肌炎(VMC)小鼠心肌细胞凋亡的抑制作用,阐明其对PI3K-Akt信号传导通路中Akt、磷酸化Akt(p-Akt)及其下游靶基因编码的Bax和Bcl-2蛋白的作用机制。方法:60只BALB/c小鼠随机分为正常对照组、病毒对照组和硒干预组(n=20)。正常对照组小鼠连续3d腹腔注射不含病毒的培养液200μL;病毒对照组小鼠腹腔注射100半数组织培养感染剂量(TCID50)柯萨奇病毒B组病毒(CVB3)液200μL,连续3d;硒干预组小鼠在病毒对照组同样的处理后灌胃给予100μg·kg-1亚硒酸钠,每日1次,连续处理14d。接种CVB3的第15天处死小鼠,TUNEL法检测心肌细胞的凋亡情况,光镜下观察心肌病理变化,Western blotting法检测心肌细胞中Akt、p-Akt、Bcl-2、Bax和Cleaved caspase-3蛋白表达水平。结果:与病毒对照组比较,硒干预组小鼠生存率明显升高(P<0.01)。硒干预组小鼠的心肌病理改变较病毒对照组减轻。硒干预组小鼠心肌细胞凋亡率低于病毒对照组(P<0.01)。与病毒对照组比较,硒干预组小鼠心肌细胞中p-Akt、Bcl-2蛋白表达水平增加,Bax、Cleaved caspase-3蛋白表达水平明显降低,Bax/Bcl-2蛋白比值下降(均P<0.01)。结论:硒对CVB3感染导致的VMC小鼠心肌细胞有保护作用,其作用机制与硒通过活化心肌细胞的PI3K-Akt信号通路、调控其下游Bcl-2和Bax蛋白表达和抑制心肌细胞凋亡有关。
Objective： To investigate the inhibitory effect of selenium on the apoptosis of myocardial cells in the mice with viral myocarditis （VMC）, and to clarify its influence in the expressions of Akt, p-Akt of PI3K-Akt signaling pathway and their down-stream protein Bax and Bcl-2. Methods： Sixty male BALB/c mice were randomly divided into blank control group, virus control group and selenium intervention group （n=20）. The mice in virus control group and selenium intervention group were intraperitoneally injected with 200μL fluid including 100 TCID50 coxsackievirus B3 （CVB3） for 3 d to establish the viral myocarditis models. The mice in blank control group were treated intraperitoneally with 200 μL fluid without virus for 3 d. The rats in selenium intervention group were given100 μg ·kg-1 sodium selenite by intragastric administration for 14 d continuously after modeling. All the mice were killed on the 15th day after the CVB3 injection. TUNEL analysis was used to detect the apoptosis of myocardial cells, and the pathological changes of myocardial cells were examined by light microscope. The expression levels of Akt, p-Akt, Bax, Bcl-2 and Cleaved caspase-3 were detected by Western blotting method. Results The survival rate of the mice in selenium intervention group was higher than that in virus control group （P〈0.01）. The pathological changes of myocardium of the rats in in selenium intervention group were improved compared with virus control group. The apoptotic rate of myocardial cells in selenium intervention group was lower than that in virus control group （P〈0.01）. Compared with virus control group, the expression levels of Bax and Cleaved caspase-3 in selenium intervention group were decreased and the expression levels of Bcl-2 and p-Akt were increased （P〈 0.01）. Conclusion： Selenium can inhibit the CVB3 virus induced apoptosis and play a protective effect on the myocardium in the mice with VMC through affecting the expressions of Akt, p-Akt of PI3K-Akt signaling pathway and regulating the down-stream Bax and Bcl-2 protein expressions and inhibiting the apoptosis of myocardial cells.
出处
《吉林大学学报（医学版）》
CAS
CSCD
北大核心
2016年第1期54-58,共5页
Journal of Jilin University：Medicine Edition
基金
吉林省科技厅青年基金资助课题(20140520022JH)
吉林省长春市科技局科研基金资助课题(2012150-12SF78)
