摘要
目的:通过制备铅中毒模型诱导原代培养神经元凋亡来探讨neuregulin1(NRG1)的抗神经元凋亡作用及机制。方法:将NRG1和(或)PI3K抑制剂Wortmannin(10μmol·L-1)加入到原代培养神经元的培养基中进行预孵育4 h,然后用醋酸铅刺激原代神经元4 h,观察NRG1的抗凋亡作用及机制。用Caspase3活力变化来检测神经元内凋亡的表达水平,同时,Western blot检测NRG1β1和p-Akt的水平。结果:在用铅刺激原代神经元后,细胞凋亡明显,表现为Caspase-3活力显著增加(P<0.05)。NRG1能抑制铅染毒引起的Caspase-3活力增加(P<0.05)。NRG1可上调p-Akt的表达,应用PI3K/Akt的抑制剂Wortmannin后,Wortmannin能拮抗NRG1的升高p-Akt及抗凋亡作用(P<0.05)。结论:NRG1显著抵抗铅诱导的神经元凋亡,PI3K/Akt途径参与介导NRG1的抗神经元凋亡作用。
ORJECTIVE To investigate the neuroprotection effect of NRG1 against PbAC-induced apoptosis in primary cul- ture neurons. METHODS The primary culture neurons were exposed to NRG1 and （or） PI3K inhibitor Wortmannin for 4 h, respectively. PbAC was then added to the cultures, which stimulated the neurons for 4 h to induce apoptosis. The anti-apoptosis effect of NRG1 and its mechanism were investigated. The expression of apoptosis was measured by Caspase 3 activity. Mean- while,the protein expressions of NRGlβ1 and p-Akt were tested by western blot. RESULTS The Caspase 3 activity increased significantly after PbAC treatment in primary culture neurons（P〈0. 05）. Pretreatment of NRG1 prevented PbAC-induced ap- optosis in primary culture neurons（P〈0. 05）. Treatment of NRG1 significantly increased the p-Akt and decreased the Caspase 3 activity,and the effects were antagonized by pretreatment with the Pi3K/Akt inhibitor, Wortmannin（P〈0. 05）. CONCLU- SION The findings suggest that NRG1 may have anti-apoptosis effect and that the PBK/Akt signaling pathway may mediate the neuroprotection of NRG1 against the apoptosis induced by PbAC.
出处
《中国医院药学杂志》
CAS
CSCD
北大核心
2014年第23期1983-1986,共4页
Chinese Journal of Hospital Pharmacy
基金
河南省教育厅科学技术研究重点项目(编号:13A310862)
国家自然科学基金项目(编号:81301174)
作者简介
崔卫刚，男，副教授，博士，研究方向：神经退行性疾病，电话：0373-3029051，E-mail：cuiweigang1978@126．com
[通讯作者]杨彩玲，女，硕士，副教授，电话：0373-4403884，E-mail：yangcailingl234@126．com
