辛伐他汀通过MEK/ERK信号转导通路上调突触素表达

Up-regulated expression of synaptophysin by simvastatin through activation of MEK/ERK signaling pathways

目的研究辛伐他汀(SV)对体外培养大鼠大脑皮层神经元突触素(SYP)的影响及信号转导机制。方法从新生Sprague-Dawley大鼠大脑皮层分离和培养神经元,4 d后分为对照组、SV处理组(2、4、8μmol/L作用48 h)、PD98059处理组和SV+PD98059处理组(先加入10μmol/L阻断剂PD98059作用30 min,再加入10μmol/L SV作用48 h)。应用免疫荧光检测法检测SYP表达,Western blot检测磷酸化丝裂原细胞外激酶(p-MEK)、磷酸化细胞外调节蛋白激酶1(p-ERK1)和磷酸化细胞外调节蛋白激酶2(p-ERK2)水平。结果免疫荧光检测显示,4μmol/L SV可明显增强SYP免疫反应性。Western blot检测显示,8μmol/L SV可显著增高SYP、p-MEK、p-ERK1和p-ERK2水平。应用PD98059可显著降低SV引起的SYP、p-MEK、p-ERK1和p-ERK2水平上调。结论SV可通过激活MEK/ERK信号转导通路上调SYP表达。

Objective To investigate the effect of simvastatin(SV)on the expression of synaptophysin(SYP)in cerebral cortex of cultured rats in vitro and its signal transduction mechanism.Methods Neurons were isolated and cultured from cerebral cortex of neonatal Sprague Dawley rats.AfteR4 days,the rats were divided into control group,SV group(processed with 2,4,8μmol/L SV foR48 h),PD98059 treatment group,and SV combined with PD98059 treatment group(firstly processed with 10μmol/L blockeRPD98059 foR30 min,and then treated with 10μmol/L SV foR48 h).The expression of SYP was detected by immunofluorescence assay,and the levels of phosphorylated mitogen-activated protein kinase(p-MEK),phosphorylated extracellulaRregulated protein kinase 1(p-ERK1)and phosphorylated extracellulaRregulated protein kinase 2(p-ERK2)were detected by Western blot.Results Immunofluorescence assay showed that 4μmol/L SV could significantly enhance the immunoreactivity of SYP.Western blot showed that 8μmol/L SV could significantly increase the levels of SYP,p-MEK,p-ERK1 and p-ERK2.PD98059 can significantly reduce up-regulation of SYP,p-MEK,p-ERK1 and p-ERK2 induced by SV.Conclusion SV can up-regulate SYP expression by activating MEK/ERK signal transduction pathway.